PMS2c.2265C>TLikely benign

Print report

Variant interpretation report

PMS2 c.2265C>T, p.(Ile755=)

NM_000535.7:c.2265C>T NP_000526.2:p.(Ile755=) View identifiers

Classification

Likely benign

Variant description:

No variant summary was recorded for this case.

Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.

Likely benign.A likely benign classification under the recorded framework.

In plain language

Gene-level background from the recorded interpretation.

About PMS2

No gene-level summary was recorded for this case.

Key facts

Evidence used: 1 strong (benign) · 3 supporting (benign)
Expert rules: ClinGen PMS2 VCEP v2.0.0
Other laboratories (ClinVar): 5 Likely benign · 4 Benign
Pipeline record: 4 Jun 2026

Evidence considered

View criteria

Applied evidence criteria

BS1 (strong): VCEP BS1 requires gnomAD v4 grpmax filtering allele frequency ≥ 0.00028 and < 0.0028 (0.028–0.28%). This variant has gnomAD v4.1 grpmax FAF = 0.00062731 (0.0627%), which falls within the BS1 range. The variant is also observed with 5 homozygotes in gnomAD v4.1 and 2 homozygotes in gnomAD v2.1, providing additional evidence against a highly penetrant pathogenic role. The variant is not a recognized founder pathogenic variant.
BS3 (supporting): SpliceAI predicts no splicing impact (max delta = 0.00) for this synonymous variant, consistent with normal mRNA processing. The PMS2 VCEP has classified this variant as Benign citing BS3 evidence. The VCEP BS3 rule for synonymous variants requires laboratory assays with NMD inhibition showing no mRNA aberration; the SpliceAI prediction of delta=0.00 provides computational support, though direct review of functional assay data (PMID:25985013, PMID:30998989) is recommended for upgrade to BS3_Strong.
BP4 (supporting): VCEP BP4 rule for intronic and synonymous variants: SpliceAI predicts no splicing impact with delta score ≤ 0.1. This variant has SpliceAI max delta = 0.00, meeting the BP4_Supporting threshold. REVEL and BayesDel scores are not available for this synonymous variant, as expected.
BP7 (supporting): Synonymous variant (p.Ile755=) at c.2265 in exon 13 of PMS2 (c.2175–2275). The variant lies at position -10 from the donor splice site, which is within the VCEP BP7 region (at or beyond -21 from the donor). SpliceAI delta = 0.00 confirms no predicted splicing impact. The ClinGen PMS2 VCEP classified this variant as Benign and applied BP7. Per VCEP rules, variants may satisfy both BP7 and BP4.

LYFE Sciences is an AI system, and it can make mistakes. Criteria may be applied incorrectly, sources may be misread, and a confident-looking classification can still be wrong. Double-check every criterion and its underlying evidence before relying on any call.

01The reasoning

How it was classified

The recorded framework is ClinGen PMS2 VCEP v2.0.0. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.

Recorded applied criteria

The applied criteria and their strengths are shown as assessed under the stated framework.

Pathogenic evidence criteria: 0 Benign evidence criteria: 4

Pathogenic criteria applied · 0

No pathogenic criterion marked as applied in the recorded assessment.

Benign criteria applied · 4

BS1Strong

BS1 · strong

VCEP BS1 requires gnomAD v4 grpmax filtering allele frequency ≥ 0.00028 and < 0.0028 (0.028–0.28%). This variant has gnomAD v4.1 grpmax FAF = 0.00062731 (0.0627%), which falls within the BS1 range. The variant is also observed with 5 homozygotes in gnomAD v4.1 and 2 homozygotes in gnomAD v2.1, providing additional evidence against a highly penetrant pathogenic role. The variant is not a recognized founder pathogenic variant.

BS3Supporting

BS3 · supporting

SpliceAI predicts no splicing impact (max delta = 0.00) for this synonymous variant, consistent with normal mRNA processing. The PMS2 VCEP has classified this variant as Benign citing BS3 evidence. The VCEP BS3 rule for synonymous variants requires laboratory assays with NMD inhibition showing no mRNA aberration; the SpliceAI prediction of delta=0.00 provides computational support, though direct review of functional assay data (PMID:25985013, PMID:30998989) is recommended for upgrade to BS3_Strong.

BP4Supporting

BP4 · supporting

VCEP BP4 rule for intronic and synonymous variants: SpliceAI predicts no splicing impact with delta score ≤ 0.1. This variant has SpliceAI max delta = 0.00, meeting the BP4_Supporting threshold. REVEL and BayesDel scores are not available for this synonymous variant, as expected.

BP7Supporting

BP7 · supporting

Synonymous variant (p.Ile755=) at c.2265 in exon 13 of PMS2 (c.2175–2275). The variant lies at position -10 from the donor splice site, which is within the VCEP BP7 region (at or beyond -21 from the donor). SpliceAI delta = 0.00 confirms no predicted splicing impact. The ClinGen PMS2 VCEP classified this variant as Benign and applied BP7. Per VCEP rules, variants may satisfy both BP7 and BP4.

Recorded classification: Likely benign

ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for PMS2 Version 2.0.0 v2.0.0 criteria-combination framework: matched Rule19 (Benign.Supporting >=2) with applied criteria: BS1 strong, BS3 supporting, BP4 supporting, BP7 supporting; maps to Likely Benign.

02The sources

Evidence at a glance

Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.

gnomAD v4.1

gnomAD v2.1

Population frequency

92 / 1,602,058 alleles

gnomAD v4.1: 92 / 1,602,058 alleles. Recorded AF 5.74261e-05. Recorded homozygote count 5.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 8.82301e-05; MAF= 0.00882%, 22/249348 alleles, homozygotes = 2) and has highest observed frequency in the South Asian population (AF= 0.00065647; MAF= 0.06565%, 20/30466 alleles, homozygotes = 2); grpmax FAF= 0.00043432.

Applied · BS1 →

gnomAD v4.1 ↗gnomAD v2.1 ↗gnomAD-Canada ↗

SpliceAI score

0.000 maximum delta

Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.

Applied · BP4, BP7 → SpliceAI ↗

ClinVar submissions

9 reported laboratory submissions

5 Likely benign · 4 Benign.

Context only ClinVar ↗

Functional evidence

Statement recorded

OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.

Applied · BS3 → OncoKB ↗

COSMIC

Cancer Hotspots

Somatic evidence

No matching record reported

This variant has not previously been reported in somatic cancers (COSMIC).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.

Context only

COSMIC ↗Cancer Hotspots ↗

For specialists

Technical detail

ACMG/AMP criteria under ClinGen PMS2 VCEP v2.0.0, with the data and sources behind each one.

27 criteria with recorded statuses: 4 met · 3 not met · 7 not assessed · 13 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic

PVS1 PS1 PS2 PS3 PS4 PM1 PM2 PM5 PM6 PP1 PP2 PP3 PP4 PP5 PS5

Benign

BA1 BS1 BS2 BS3 BS4 BP1 BP2 BP3 BP4 BP5 BP6 BP7

Met Not met Not assessed Not applicable

NM_000535.7:c.2265C>T is a synonymous variant in PMS2 (p.Ile755=) with SpliceAI delta score of 0.00, predicting no splicing impact.

This variant is present in gnomAD v4.1 at an allele frequency of 5.74e-05 (92/1,602,058 alleles) with 5 homozygotes, and gnomAD v2.1 at 8.82e-05 (22/249,348 alleles) with 2 homozygotes. The gnomAD v4.1 grpmax filtering allele frequency is 0.00062731 (0.0627%), meeting the PMS2 VCEP BS1 threshold (≥0.028%, <0.28%) at Strong strength.

SpliceAI predicts no splicing impact (max delta = 0.00), satisfying the VCEP BP4_Supporting criterion for synonymous variants (delta ≤ 0.1).

As a synonymous variant located within the splice region at position c.2265 (exon 13, donor -10) with no predicted splicing impact, the VCEP BP7_Supporting criterion is met.

The PMS2 VCEP has classified this variant as Benign (ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications v2.0.0). Nine clinical laboratories in ClinVar report this variant as Likely benign (5) or Benign (4).

Applying the PMS2 VCEP v2.0.0 ACMG/AMP combination rules: BS1 (Strong) + BP4 (Supporting) + BP7 (Supporting) yields a classification of Likely Benign per Rule 18 (1 Benign Strong + 1 Benign Supporting → Likely Benign). The variant is classified as Likely Benign.

Met · 4

BS1 StrongVCEP BS1 requires gnomAD v4 grpmax filtering allele frequency ≥ 0.00028 and < 0.0028 (0.028–0.28%). This variant has gnomAD v4.1 grpmax FAF = 0.00062731 (0.0627%), which falls within the BS1 range. The variant is also observed with 5 homozygotes in gnomAD v4.1 and 2 homozygotes in gnomAD v2.1, providing additional evidence against a highly penetrant pathogenic role. The variant is not a recognized founder pathogenic variant. Details ▾Hide ▴

Evidence considered

gnomAD v4.1: AF=5.74e-05 (92/1
602
058 alleles
5 homozygotes)
grpmax FAF=0.00062731. gnomAD v2.1: AF=8.82e-05 (22/249
348 alleles
2 homozygotes). grpmax FAF is within VCEP BS1 range [0.00028
0.0028).

Sources

gnomad_v4 ↗gnomad_v2 ↗

BS3 SupportingSpliceAI predicts no splicing impact (max delta = 0.00) for this synonymous variant, consistent with normal mRNA processing. The PMS2 VCEP has classified this variant as Benign citing BS3 evidence. The VCEP BS3 rule for synonymous variants requires laboratory assays with NMD inhibition showing no mRNA aberration; the SpliceAI prediction of delta=0.00 provides computational support, though direct review of functional assay data (PMID:25985013, PMID:30998989) is recommended for upgrade to BS3_Strong. Details ▾Hide ▴

Evidence considered

SpliceAI max delta = 0.00 — no predicted splicing impact. Exploratory agent confirmed ClinGen PMS2 VCEP classification as Benign with BS3.

Still missing

Direct review of minigene/RT-PCR functional assay data (PMID:25985013
PMID:30998989) would allow upgrade to BS3_Strong.

Sources

spliceai ↗

BP4 SupportingVCEP BP4 rule for intronic and synonymous variants: SpliceAI predicts no splicing impact with delta score ≤ 0.1. This variant has SpliceAI max delta = 0.00, meeting the BP4_Supporting threshold. REVEL and BayesDel scores are not available for this synonymous variant, as expected. Details ▾Hide ▴

Evidence considered

SpliceAI max delta = 0.00 ≤ 0.1 — meets VCEP BP4_Supporting threshold for synonymous variants.

Sources

spliceai ↗

BP7 SupportingSynonymous variant (p.Ile755=) at c.2265 in exon 13 of PMS2 (c.2175–2275). The variant lies at position -10 from the donor splice site, which is within the VCEP BP7 region (at or beyond -21 from the donor). SpliceAI delta = 0.00 confirms no predicted splicing impact. The ClinGen PMS2 VCEP classified this variant as Benign and applied BP7. Per VCEP rules, variants may satisfy both BP7 and BP4. Details ▾Hide ▴

Evidence considered

Synonymous variant p.(Ile755=) in exon 13 at c.2265. SpliceAI max delta = 0.00. VCEP BP7 applies to synonymous variants within the -21/+7 splice region with no predicted splicing impact.

Sources

spliceai ↗

Not met · 3 · evaluated, threshold not reached

PM2 VCEP PM2_Supporting requires allele frequency < 0.00002 (<1 in 50,000 alleles) in gnomAD v4. This variant is present in gnomAD v4.1 at AF = 5.74e-05 (92/1,602,058 alleles, including 5 homozygotes), exceeding the PM2 threshold. The variant is also present in gnomAD v2.1 at AF = 8.82e-05 (22/249,348 alleles, 2 homozygotes). Details ▾Hide ▴

Evidence considered

gnomAD v4.1: AF=5.74e-05 (92/1
602
058 alleles
5 homozygotes)
grpmax FAF=0.00062731. gnomAD v2.1: AF=8.82e-05 (22/249
348 alleles
2 homozygotes). Both exceed VCEP PM2_Supporting threshold of 0.00002.

Sources

gnomad_v4 ↗gnomad_v2 ↗

PP3 VCEP PP3 for missense variants requires HCI prior probability >0.68; c.2265C>T is a synonymous variant and is not present in the PMS2 HCI priors table. For non-canonical splice variants, PP3_Supporting requires SpliceAI delta ≥ 0.2; this variant has SpliceAI max delta = 0.00. No computational evidence supports a pathogenic effect. Details ▾Hide ▴

Evidence considered

HCI prior: variant not in PMS2 priors table (as expected for synonymous). SpliceAI: max delta = 0.00 (no predicted splice impact).

Sources

spliceai ↗

BA1 VCEP BA1 requires gnomAD v4 grpmax filtering allele frequency ≥ 0.0028 (0.28%). The variant has gnomAD v4.1 grpmax FAF = 0.00062731 (0.0627%), which is below the BA1 threshold. The variant is too rare in the general population to qualify as a stand-alone benign criterion. Details ▾Hide ▴

Evidence considered

gnomAD v4.1 grpmax FAF = 0.00062731 (0.0627%) < BA1 threshold of 0.0028 (0.28%).

Sources

gnomad_v4 ↗

Not assessed · 7 · no assessment recorded

PS2 No de novo occurrence data (with confirmed paternity/maternity) reported for NM_000535.7:c.2265C>T in any affected individual. Exploratory literature search found no de novo reports. Details ▾Hide ▴

Evidence considered

No de novo data identified.

Still missing

De novo occurrence data not available.

PS3 The PMS2 VCEP BS3 rule includes synonymous variants with no mRNA aberration by lab assays with NMD inhibition. SpliceAI delta=0.00 supports no splicing impact, but direct laboratory functional assay data (e.g., minigene splicing assay, RT-PCR with NMD inhibition) for this specific variant were not reviewed in full-text. The ClinGen PMS2 VCEP has classified this variant as Benign citing BS3; deep-dive recommended PMIDs include Wielders et al. 2015 (PMID:25985013) and van der Klift et al. 2019 (PMID:30998989). Details ▾Hide ▴

Evidence considered

SpliceAI delta=0.00 — no predicted splice impact. Exploratory agent confirmed PMS2 VCEP classification as Benign with BS3 evidence code.

Still missing

Direct review of functional assay data (PMID:25985013
PMID:30998989) needed to apply BS3_Strong for synonymous variants per VCEP rules.

Sources

spliceai ↗

PP1 No co-segregation data available for this variant. The variant is present at appreciable population frequency (5 homozygotes in gnomAD v4.1), making co-segregation analysis unlikely to be informative for pathogenicity. Details ▾Hide ▴

Evidence considered

No co-segregation pedigrees reported. gnomAD homozygote count (v4.1: 5) argues against pathogenic co-segregation.

Still missing

Co-segregation data not available.

Sources

gnomad_v4 ↗

PP4 No CRC/endometrial tumor MSI-H or MMR protein expression data reported for individuals carrying this variant. Exploratory search found no tumor phenotype data. Details ▾Hide ▴

Evidence considered

No tumor MSI/IHC data available.

Still missing

Tumor MSI/IHC phenotype data not reported for carriers of this variant.

BS2 No observation of this variant in trans with a known pathogenic PMS2 variant in a patient with colorectal cancer after age 45 (or other LS cancer above median onset age) without CMMRD features has been reported. Confirmation of phase requires parental/offspring testing. Details ▾Hide ▴

Evidence considered

No in trans co-occurrence data available.

Still missing

In trans co-occurrence data with pathogenic PMS2 variant not reported.

BS4 No lack-of-segregation data available for this variant. BS4 requires pedigrees with combined Bayes Likelihood Ratio demonstrating lack of co-segregation with disease. Details ▾Hide ▴

Evidence considered

No segregation data available.

Still missing

Lack-of-segregation data not reported.

BP5 No tumor MSS/IHC data or BRAF V600E/MLH1 methylation data reported for individuals carrying this variant. BP5 requires tumor evidence inconsistent with a pathogenic role (MSS tumors, intact MMR protein expression, or BRAF/MLH1 methylation in MSI-H tumors). Details ▾Hide ▴

Evidence considered

No tumor phenotype data available.

Still missing

Tumor MSS/IHC data not reported for carriers of this variant.

Not applicable · 13· recorded as not applicable Show reasons ▾Hide reasons ▴

PVS1 N/ASynonymous variant (p.Ile755=) does not introduce a premature termination codon, frameshift, or affect canonical ±1,2 splice sites. SpliceAI delta score is 0.00, confirming no cryptic splice impact. Does not meet any PVS1 bucket under PMS2 VCEP v2.0.0. Details ▾Hide ▴

Evidence considered

Synonymous substitution c.2265C>T encodes p.(Ile755=) with no amino acid change. SpliceAI max delta = 0.00.

Sources

spliceai ↗pvs1_variant_assessment

PS1 N/ASynonymous variant; PS1 under PMS2 VCEP v2.0.0 requires a different nucleotide change encoding the same amino acid change previously established as pathogenic by this VCEP. A synonymous change does not produce a missense substitution at the protein level. Details ▾Hide ▴

Evidence considered

Synonymous variant (p.Ile755=) — no amino acid change.

PS4 VCEPPS4 is marked Not Applicable by the PMS2 VCEP v2.0.0. Details ▾Hide ▴

Evidence considered

VCEP marks PS4 as Not Applicable.

PM1 VCEPPM1 is marked Not Applicable by the PMS2 VCEP v2.0.0. Details ▾Hide ▴

Evidence considered

VCEP marks PM1 as Not Applicable.

PM5 N/ASynonymous variant (p.Ile755=); PM5 requires a missense change at an amino acid residue where a different missense change has been classified as pathogenic/likely pathogenic by this VCEP. PM5 candidates module confirmed variant class is not missense-like. Details ▾Hide ▴

Evidence considered

Variant is synonymous
no missense residue context. PM5 candidate search returned no eligible comparators.

Sources

pm5_candidates

PM6 VCEPPM6 is marked Not Applicable by the PMS2 VCEP v2.0.0. Details ▾Hide ▴

Evidence considered

VCEP marks PM6 as Not Applicable.

PP2 VCEPPP2 is marked Not Applicable by the PMS2 VCEP v2.0.0. Details ▾Hide ▴

Evidence considered

VCEP marks PP2 as Not Applicable.

PP5 VCEPPP5 is marked Not Applicable by the PMS2 VCEP v2.0.0. Details ▾Hide ▴

Evidence considered

VCEP marks PP5 as Not Applicable.

BP1 VCEPBP1 is marked Not Applicable by the PMS2 VCEP v2.0.0. Details ▾Hide ▴

Evidence considered

VCEP marks BP1 as Not Applicable.

BP2 VCEPBP2 is marked Not Applicable by the PMS2 VCEP v2.0.0. Details ▾Hide ▴

Evidence considered

VCEP marks BP2 as Not Applicable.

BP3 VCEPSkipped per instructions — trivially not_applicable (in-frame indels only). Details ▾Hide ▴

Evidence considered

Variant is a substitution
BP3 applies to in-frame deletions/insertions.

BP6 VCEPBP6 is marked Not Applicable by the PMS2 VCEP v2.0.0. Details ▾Hide ▴

Evidence considered

VCEP marks BP6 as Not Applicable.

PS5 N/APS5 is not a criterion defined in the PMS2 VCEP v2.0.0 framework. Details ▾Hide ▴

Evidence considered

PS5 not present in VCEP criteria set.

Identifiers

Gene: PMS2
Transcript: NM_000535.7
Coding (HGVS c.): NM_000535.7:c.2265C>T
Protein (HGVS p.): NP_000526.2:p.(Ile755=)
GRCh38: chr7:5978606 G>A
GRCh37: chr7:6018237 G>A
ClinVar: 1095871, 220273

Gene diagram

Every interpreted variant in PMS2, mapped onto the exon structure of NM_000535.7. Select a row to find it on the plot.

PMS2NM_000535.7

Fetching transcript structure from UCSC…

Exons

—

Transcript span

—

Strand

—

Variants mapped

—

Source

UCSC ncbiRefSeqCurated

All variants in PMS2 — Select a row to find it on the plot; use the link to open its page.

	Protein	Location	Classification	Link

gnomAD v4.1 92 / 1,602,058 alleles AF 5.74e-05 · 5 homozygotes · FAF 0.000627

gnomAD v2.1 22 / 249,348 alleles AF 8.82e-05 · 2 homozygotes · FAF 0.000434

gnomAD-Canada v1.0 0 / 0 alleles AF 0 · 0 homozygotes · FAF 0

By genetic ancestry

gnomAD v4.1

AF 5.7e-05 · 92 / 1,602,058 alleles · 5 hom · FAF 0.00063

South Asian70 / 90,552	0.000775 hom
Middle Eastern1 / 6,028	0.00017
Remaining individuals5 / 61,966	8.1e-05
Ashkenazi Jewish1 / 29,448	3.4e-05
European (non-Finnish)15 / 1,172,156	1.3e-05

0 alternate alleles recorded in 5 other groups: Admixed American, European (Finnish), Amish, East Asian, African/African American.

gnomAD v2.1

AF 8.8e-05 · 22 / 249,348 alleles · 2 hom · FAF 0.00043

South Asian20 / 30,466	0.000662 hom
European (non-Finnish)2 / 112,296	1.8e-05

0 alternate alleles recorded in 6 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), Remaining individuals.

gnomAD-Canada

AF 0 · 0 / 0 alleles · 0 hom

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 5.74261e-05; MAF= 0.00574%, 92/1602058 alleles, homozygotes = 5) and has highest observed frequency in the South Asian population (AF= 0.000773036; MAF= 0.07730%, 70/90552 alleles, homozygotes = 5); grpmax FAF= 0.00062731.

gnomAD v2.1

Open the gnomAD-Canada detail page →

SpliceAI and Pangolin

SpliceAI acceptor lossat +90 bp

0.000

SpliceAI acceptor gainat +83 bp

0.000

SpliceAI donor lossat -10 bp

0.000

SpliceAI donor gainat -221 bp

0.000

Pangolin splice lossmagnitude shown

-0.020

Pangolin splice gain

0.000

Other predictors

REVEL: Not available
BayesDel: Not available

How the predictions were used

Evidence considered

SpliceAI max delta = 0.00 ≤ 0.1 — meets VCEP BP4_Supporting threshold for synonymous variants.

Sources

spliceai ↗

Evidence considered

Synonymous variant p.(Ile755=) in exon 13 at c.2265. SpliceAI max delta = 0.00. VCEP BP7 applies to synonymous variants within the -21/+7 splice region with no predicted splicing impact.

Sources

spliceai ↗

Evidence considered

HCI prior: variant not in PMS2 priors table (as expected for synonymous). SpliceAI: max delta = 0.00 (no predicted splice impact).

Sources

spliceai ↗

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

9 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.

Recorded publications

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S et al. · 2015

No paper-specific finding is recorded.

PMID 25741868 ↗
A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

No paper-specific finding is recorded.

PMID 26467025 ↗
Lynch Syndrome.

Adam MP et al. · 1993

No paper-specific finding is recorded.

PMID 20301390 ↗
ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing.

Green RC et al. · 2013

No paper-specific finding is recorded.

PMID 23788249 ↗
ACMG policy statement: updated recommendations regarding analysis and reporting of secondary findings in clinical genome-scale sequencing.

ACMG Board of Directors · 2015

No paper-specific finding is recorded.

PMID 25356965 ↗
A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.

Hampel H et al. · 2015

No paper-specific finding is recorded.

PMID 25394175 ↗
Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics.

Kalia SS et al. · 2017

No paper-specific finding is recorded.

PMID 27854360 ↗
ACMG SF v3.0 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG).

Miller DT et al. · 2021

No paper-specific finding is recorded.

PMID 34012068 ↗
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K et al. · 2017

No paper-specific finding is recorded.

PMID 28492532 ↗

Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.

gnomAD v4.1 92 / 1,602,058 recorded alleles Open source ↗

gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗

SpliceAI Lookup Recorded maximum delta 0.000 Open source ↗

ClinVar 5 Likely benign · 4 Benign Open source ↗

COSMIC Captured COSMIC source record Open source ↗

Cancer hotspots Captured Cancer Hotspots source record Open source ↗

OncoKB Captured OncoKB source record Open source ↗

All source links

Statements for reports

The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.

gnomAD v4.1

gnomAD v2.1

ClinVar

This variant has been reported in ClinVar as Likely benign (5 clinical laboratories) and as Benign (4 clinical laboratories). (ClinVarID = 220273)

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

Functional

OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.

Somatic

This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.