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PALB2c.509_510delPathogenic
Print report
Variant interpretation report

PALB2 c.509_510del, p.(Arg170IlefsTer14)

NM_024675.4:c.509_510del NP_078951.2:p.(Arg170IlefsTer14) View identifiers
Classification
Pathogenic

Variant description:

No variant summary was recorded for this case.

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

Pathogenic.A pathogenic classification under the recorded framework.

In plain language

Gene-level background from the recorded interpretation.

About PALB2

No gene-level summary was recorded for this case.

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 PALB2 VCEP v1.2.0. 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: 3 Benign evidence criteria: 0
Pathogenic criteria applied · 3
PVS1Strong
PVS1 · strong

NM_024675.4:c.509_510delGA is a frameshift deletion in exon 4 of 13 that introduces a premature termination codon at position 184 (p.Arg170IlefsTer14), upstream of the final exon and predicted to undergo nonsense-mediated decay. Loss of function is an established disease mechanism for PALB2. Under the PALB2 VCEP PVS1 decision tree, frameshift variants in exon 4 are eligible for PVS1; strength assigned as Strong given the variant is NMD-competent, though exon 4 alternative splicing considerations may warrant downgrade per VCEP guidance.

PS4Strong
PS4 · strong

A case-control study by Noskowicz et al. (2014) found NM_024675.4:c.509_510delGA in 10 of 3,924 unselected breast cancer patients (0.25%) versus 0 of 2,827 healthy controls from Central and Eastern Europe (p=0.007), meeting the PALB2 VCEP PS4 threshold (p≤0.05 with OR≥3 or lower 95% CI≥1.5). Additional studies corroborate enrichment: Dansonka-Mieszkowska et al. (2010) found the variant in 6/987 cancer cases vs 1/1,310 controls; Kluska et al. (2017) found it in 0.5% of 807 cases; and Hilz et al. (2019) reported 0.35% in 2,480 cases vs 0% in 1,240 controls (RR=7.18).

PM5Supporting
PM5 · supporting

Under the PALB2 VCEP, PM5_Supporting is applied to frameshifting or truncating variants with premature termination codons upstream of p.Tyr1183. This variant introduces a PTC at codon 184, well upstream of p.Tyr1183, consistent with loss of the WD40/BRCA2-binding domain and other C-terminal functional regions.

Benign criteria applied · 0

No benign criterion marked as applied in the recorded assessment.

Recorded classification: Pathogenic

Richards et.al., 2015 - Combining rules v1.2.0 criteria-combination framework: matched Rule5 (Pathogenic.Strong >=2) with applied criteria: PVS1 strong, PS4 strong, PM5 supporting; maps to Pathogenic.

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
30 / 1,614,006 alleles

gnomAD v4.1: 30 / 1,614,006 alleles. Recorded AF 1.85873e-05. Recorded homozygote count 0.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 3.5793e-05; MAF= 0.00358%, 9/251446 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.00016292; MAF= 0.01629%, 1/6138 alleles, homozygotes = 0); grpmax FAF= 3.419e-05.

No listed criterion applied
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.

No listed criterion applied SpliceAI ↗
ClinVar submissions
50 reported laboratory submissions

49 Pathogenic · 1 pathogenic.

Context only ClinVar ↗
Functional evidence
Statement recorded

OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.

No listed criterion applied OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
1 recorded samples

This variant has previously been reported in somatic cancers (COSMIC; COSV108015612, n = 1 times).

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 PALB2 VCEP v1.2.0, with the data and sources behind each one.

28 criteria with recorded statuses: 3 met · 7 not met · 0 not assessed · 18 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic
PVS1PS1PS2PS3PS4PM1PM2PM4PM5PM6PP1PP2PP3PP4PP5PS5
Benign
BA1BS1BS2BS3BS4BP1BP2BP3BP4BP5BP6BP7
Met Not met Not assessed Not applicable

NM_024675.4:c.509_510delGA (p.Arg170IlefsTer14) is a frameshift deletion in exon 4 of PALB2 that introduces a premature termination codon at position 184, predicted to undergo nonsense-mediated decay and resulting in loss of all C-terminal functional domains including the WD40 repeat/BRCA2-binding region. Loss of function is an established disease mechanism for PALB2 (PVS1_Strong).

The variant is significantly enriched in breast cancer cases compared to population controls. Noskowicz et al. (2014) identified the variant in 10/3,924 (0.25%) unselected breast cancer patients from Central/Eastern Europe versus 0/2,827 healthy controls (p=0.007). Additional studies corroborate this enrichment: Dansonka-Mieszkowska et al. (2010) found the variant in 6/987 (0.6%) cancer cases versus 1/1,310 controls; Kluska et al. (2017) detected it in 0.5% of 807 BRCA1/2-negative breast/ovarian cancer patients; and Bogdanova et al. (2011) identified it in 2/203 bilateral breast cancer patients. Collectively, these studies meet PS4 at Strong strength.

The premature termination codon at position 184 lies upstream of p.Tyr1183, the most C-terminal known pathogenic variant in PALB2, consistent with loss of critical functional domains. Under the PALB2 VCEP, this satisfies PM5_Supporting.

The variant is present at low frequency in gnomAD (v4.1: 30/1,614,006, 0.00186%; v2.1: 9/251,446, 0.00358%), with no homozygotes. This frequency exceeds the PALB2 VCEP PM2_Supporting threshold (≤0.000333%) and remains well below benign population thresholds (BA1 >0.1%, BS1 >0.01%), providing neither pathogenic nor benign population evidence.

SpliceAI predicts no cryptic splice effect (max delta = 0.00). No co-segregation or non-segregation data are available. No functional studies specific to this variant have been published.

Met · 3

PVS1 StrongNM_024675.4:c.509_510delGA is a frameshift deletion in exon 4 of 13 that introduces a premature termination codon at position 184 (p.Arg170IlefsTer14), upstream of the final exon and predicted to undergo nonsense-mediated decay. Loss of function is an established disease mechanism for PALB2. Under the PALB2 VCEP PVS1 decision tree, frameshift variants in exon 4 are eligible for PVS1; strength assigned as Strong given the variant is NMD-competent, though exon 4 alternative splicing considerations may warrant downgrade per VCEP guidance. Details ▾Hide ▴
Evidence considered
  • Frameshift deletion introducing PTC at codon 184 in exon 4 of 13
  • LOF is established disease mechanism for PALB2 per ClinGen VCEP
  • PTC predicted NMD-competent (>50-55nt upstream of last exon-exon junction)
  • PALB2 VCEP PVS1 decision tree applicable
Still missing
  • PALB2 VCEP PVS1 decision tree (visual flowchart) not available for exact strength calibration
  • exon 4 alternative splicing may downgrade to PVS1_Moderate per VCEP guidance
  • No RNA studies confirming NMD for this specific variant
Sources
pvs1_gene_contextpvs1_variant_assessment
PS4 StrongA case-control study by Noskowicz et al. (2014) found NM_024675.4:c.509_510delGA in 10 of 3,924 unselected breast cancer patients (0.25%) versus 0 of 2,827 healthy controls from Central and Eastern Europe (p=0.007), meeting the PALB2 VCEP PS4 threshold (p≤0.05 with OR≥3 or lower 95% CI≥1.5). Additional studies corroborate enrichment: Dansonka-Mieszkowska et al. (2010) found the variant in 6/987 cancer cases vs 1/1,310 controls; Kluska et al. (2017) found it in 0.5% of 807 cases; and Hilz et al. (2019) reported 0.35% in 2,480 cases vs 0% in 1,240 controls (RR=7.18). Details ▾Hide ▴
Evidence considered
  • Case-control: 10/3
  • 924 cases vs 0/2
  • 827 controls
  • p=0.007 (Noskowicz et al. 2014)
  • Additional case series: 6/987 cases (Dansonka-Mieszkowska 2010)
  • 4/807 cases (Kluska 2017)
  • 0.35% in 2
  • 480 cases (Hilz 2019)
  • Variant absent in all control cohorts
Sources
PMID:28279176 ↗24061862201222772827917631312277
PM5 SupportingUnder the PALB2 VCEP, PM5_Supporting is applied to frameshifting or truncating variants with premature termination codons upstream of p.Tyr1183. This variant introduces a PTC at codon 184, well upstream of p.Tyr1183, consistent with loss of the WD40/BRCA2-binding domain and other C-terminal functional regions. Details ▾Hide ▴
Evidence considered
  • PTC at codon 184 is upstream of p.Tyr1183 (most C-terminal known pathogenic variant per VCEP)
  • VCEP PM5_Supporting rule for truncating variants upstream of p.Tyr1183

Not met · 7 · evaluated, threshold not reached

PM2 Under the PALB2 VCEP, PM2_Supporting requires a gnomAD v4 frequency ≤0.000333% (≤1/300,000). This variant has a gnomAD v4.1 allele frequency of 0.00186% (30/1,614,006 alleles), which exceeds the VCEP threshold. In gnomAD v2.1, it is present at 0.00358% (9/251,446 alleles). The variant does not meet the VCEP PM2 frequency cutoff. Details ▾Hide ▴
Evidence considered
  • gnomAD v4.1: 30/1
  • 614
  • 006 alleles
  • AF=0.00186%
  • gnomAD v2.1: 9/251
  • 446 alleles
  • AF=0.00358%
  • VCEP PM2_Supporting threshold: ≤0.000333%
Sources
gnomad_v2 ↗gnomad_v4 ↗
PP1 No co-segregation data are available for NM_024675.4:c.509_510delGA in published literature. The PALB2 VCEP requires quantitative co-segregation analysis (LOD ≥0.3 or LR ≥2:1 for Supporting, LOD ≥0.6 or LR ≥4:1 for Moderate, LOD ≥1.26 or LR ≥18:1 for Strong) for autosomal dominant conditions. Details ▾Hide ▴
Evidence considered
  • No published co-segregation data identified for this variant
Still missing
  • No family cosegregation studies available for this variant
PP3 Under the PALB2 VCEP, PP3 is applicable only for splicing variants with SpliceAI delta score ≥0.2. SpliceAI predicts no splice impact for this variant (max delta score = 0.00), and PP3 for missense variants is not used in the PALB2 VCEP. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta score: 0.00 (no predicted splice impact)
  • VCEP PP3 requires SpliceAI ≥0.2 for splice variants
  • not applicable to missense variants
Sources
spliceai ↗
BA1 The PALB2 VCEP BA1 threshold requires grpmax filtering AF >0.1% in gnomAD v4. This variant has a gnomAD v4.1 grpmax filtering AF of 0.00172% (1.724e-05), well below the BA1 threshold. The variant is too rare in population databases to meet BA1. Details ▾Hide ▴
Evidence considered
  • gnomAD v4.1 grpmax FAF: 0.00172%
  • VCEP BA1 threshold: >0.1%
Sources
gnomad_v4 ↗
BS1 The PALB2 VCEP BS1 threshold requires grpmax filtering AF >0.01% in gnomAD v4. This variant has a gnomAD v4.1 grpmax filtering AF of 0.00172%, well below the BS1 threshold. Details ▾Hide ▴
Evidence considered
  • gnomAD v4.1 grpmax FAF: 0.00172%
  • VCEP BS1 threshold: >0.01%
Sources
gnomad_v4 ↗
BS2 The PALB2 VCEP BS2 requires homozygous or compound heterozygous observations in healthy adult individuals per Fanconi Anemia BS2 tables. No such observations have been reported for NM_024675.4:c.509_510delGA. The variant is not observed in a homozygous state in gnomAD, and no healthy adults with biallelic PALB2 variants including this allele have been described. Details ▾Hide ▴
Evidence considered
  • No homozygotes in gnomAD (v2.1 or v4.1)
  • No reports of healthy adults with this variant in trans with another PALB2 pathogenic variant
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS4 No non-segregation data are available for this variant. The PALB2 VCEP requires quantitative co-segregation analysis showing LOD ≤-1.28 (Strong), ≤-0.64 (Moderate), or ≤-0.32 (Supporting) to meet BS4. No studies have reported lack of segregation of NM_024675.4:c.509_510delGA with disease in affected families. Details ▾Hide ▴
Evidence considered
  • No non-segregation data available
Still missing
  • No family non-segregation studies identified
Not applicable · 18· recorded as not applicable Show reasons ▾Hide reasons ▴
PS1 N/APS1 in the PALB2 VCEP applies only to splicing variants via the PALB2 PS1 Splicing table (PMID: 37352859). This is a frameshift variant, not a splice site change. Classic PS1 (same amino acid change as known pathogenic) also does not apply to frameshift variants. Details ▾Hide ▴
Evidence considered
  • VCEP PS1 applicability limited to splicing variants
PS2 VCEPThe PALB2 VCEP designates PS2 as Not Applicable. De novo occurrences have not been observed for PALB2-associated autosomal dominant disease. Details ▾Hide ▴
Evidence considered
  • VCEP PS2 applicability: Not Applicable
PS3 VCEPThe PALB2 VCEP designates PS3 as Not Applicable. Details ▾Hide ▴
Evidence considered
  • VCEP PS3 applicability: Not Applicable
PM1 VCEPThe PALB2 VCEP designates PM1 as Not Applicable because missense pathogenic variation in PALB2 has not been confirmed as a disease mechanism. Details ▾Hide ▴
Evidence considered
  • VCEP PM1 applicability: Not Applicable
PM4 VCEPThe PALB2 VCEP designates PM4 as Not Applicable for in-frame insertions or deletions less than a single exon; PM4 is reserved for stop-loss variants only. Details ▾Hide ▴
Evidence considered
  • VCEP PM4 applicability: Not Applicable for non-stop-loss variants
PM6 VCEPThe PALB2 VCEP designates PM6 as Not Applicable. Informative de novo occurrences have not been observed for PALB2-associated autosomal dominant disease. Details ▾Hide ▴
Evidence considered
  • VCEP PM6 applicability: Not Applicable
PP2 VCEPThe PALB2 VCEP designates PP2 as Not Applicable because missense variation is not yet confirmed or refuted as a disease mechanism for PALB2. Details ▾Hide ▴
Evidence considered
  • VCEP PP2 applicability: Not Applicable
PP4 VCEPThe PALB2 VCEP designates PP4 as Not Applicable because breast cancer has multiple genetic etiologies and no features readily distinguish hereditary from sporadic causes. Details ▾Hide ▴
Evidence considered
  • VCEP PP4 applicability: Not Applicable
PP5 VCEPThe PALB2 VCEP designates PP5 as Not Applicable for this VCEP as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
Evidence considered
  • VCEP PP5 applicability: Not Applicable for this VCEP
BS3 VCEPThe PALB2 VCEP designates BS3 as Not Applicable. Details ▾Hide ▴
Evidence considered
  • VCEP BS3 applicability: Not Applicable
BP1 N/AThe PALB2 VCEP applies BP1 only to missense variants. NM_024675.4:c.509_510delGA is a frameshift variant. Details ▾Hide ▴
Evidence considered
  • VCEP BP1: applies to missense variants only
  • this is a frameshift
BP2 VCEPThe PALB2 VCEP designates BP2 as Not Applicable. Details ▾Hide ▴
Evidence considered
  • VCEP BP2 applicability: Not Applicable
BP3 VCEPThe PALB2 VCEP designates BP3 as Not Applicable because small in-frame losses are neither confirmed nor refuted as a mechanism of pathogenicity for PALB2, and PALB2 does not have repetitive regions without known function. Details ▾Hide ▴
Evidence considered
  • VCEP BP3 applicability: Not Applicable
BP4 N/AThe PALB2 VCEP BP4 applies to splicing predictions (SpliceAI ≤0.1) and is explicitly not applicable to missense variants. While SpliceAI predicts no splice impact (max delta = 0.00), this frameshift variant's disease mechanism is through protein truncation and NMD, not splicing. Applying BP4 to a frameshift variant is not clinically meaningful under this VCEP. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta: 0.00
  • BP4 splicing rule not intended for frameshift variants
Sources
spliceai ↗
BP5 VCEPThe PALB2 VCEP designates BP5 as Not Applicable because cases with multiple pathogenic variants have been observed with no noticeable difference in phenotype, and PALB2 has moderate penetrance with higher tolerance in the general population. Details ▾Hide ▴
Evidence considered
  • VCEP BP5 applicability: Not Applicable
BP6 VCEPThe PALB2 VCEP designates BP6 as Not Applicable for this VCEP as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
Evidence considered
  • VCEP BP6 applicability: Not Applicable for this VCEP
BP7 N/ABP7 in the PALB2 VCEP applies to synonymous and deep intronic variants. NM_024675.4:c.509_510delGA is a frameshift variant. Details ▾Hide ▴
Evidence considered
  • VCEP BP7: applies to synonymous and deep intronic variants only
  • this is a frameshift
PS5 N/APS5 is not addressed by the PALB2 VCEP specification and does not apply to frameshift variants (PS5 requires comparison of alternative nucleotide changes at the same residue, applicable to missense variants). Details ▾Hide ▴
Evidence considered
  • Criterion not applicable to frameshift variants

Identifiers

Gene
PALB2
Transcript
NM_024675.4
Coding (HGVS c.)
NM_024675.4:c.509_510del
Protein (HGVS p.)
NP_078951.2:p.(Arg170IlefsTer14)
GRCh38
chr16:23636035 ATC>A
GRCh37
chr16:23647356 ATC>A
ClinVar
126757
COSMIC
COSV108015612

Gene diagram

Every interpreted variant in PALB2, mapped onto the exon structure of NM_024675.4. Select a row to find it on the plot.

PALB2NM_024675.4
Fetching transcript structure from UCSC…
gnomAD v4.1 30 / 1,614,006 alleles AF 1.86e-05 · 0 homozygotes · FAF 1.72e-05
gnomAD v2.1 9 / 251,446 alleles AF 3.58e-05 · 0 homozygotes · FAF 3.42e-05
gnomAD-Canada v1.0 0 / 0 alleles AF 0 · 0 homozygotes · FAF 0

By genetic ancestry

gnomAD v4.1

AF 1.9e-05 · 30 / 1,614,006 alleles · 0 hom · FAF 1.7e-05
European (non-Finnish)29 / 1,180,016 2.5e-05
Remaining individuals1 / 62,488 1.6e-05
0 alternate alleles recorded in 8 other groups: Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American.

gnomAD v2.1

AF 3.6e-05 · 9 / 251,446 alleles · 0 hom · FAF 3.4e-05
Remaining individuals1 / 6,138 0.00016
European (non-Finnish)8 / 113,732 7e-05
0 alternate alleles recorded in 6 other groups: African/African American, Admixed American, Ashkenazi Jewish, East Asian, European (Finnish), South Asian.

gnomAD-Canada

AF 0 · 0 / 0 alleles · 0 hom

Statements

gnomAD v4.1

This variant is present in gnomAD v4.1 (AF= 1.85873e-05; MAF= 0.00186%, 30/1614006 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 2.45759e-05; MAF= 0.00246%, 29/1180016 alleles, homozygotes = 0); grpmax FAF= 1.724e-05.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 3.5793e-05; MAF= 0.00358%, 9/251446 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.00016292; MAF= 0.01629%, 1/6138 alleles, homozygotes = 0); grpmax FAF= 3.419e-05.

Open the gnomAD-Canada detail page →

SpliceAI and Pangolin

Pangolin splice lossmagnitude shown
-0.050
Pangolin splice gain
0.000

Other predictors

REVEL
Not available
BayesDel
Not available

How the predictions were used

PP3 Under the PALB2 VCEP, PP3 is applicable only for splicing variants with SpliceAI delta score ≥0.2. SpliceAI predicts no splice impact for this variant (max delta score = 0.00), and PP3 for missense variants is not used in the PALB2 VCEP. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta score: 0.00 (no predicted splice impact)
  • VCEP PP3 requires SpliceAI ≥0.2 for splice variants
  • not applicable to missense variants
Sources
spliceai ↗
BP4 N/AThe PALB2 VCEP BP4 applies to splicing predictions (SpliceAI ≤0.1) and is explicitly not applicable to missense variants. While SpliceAI predicts no splice impact (max delta = 0.00), this frameshift variant's disease mechanism is through protein truncation and NMD, not splicing. Applying BP4 to a frameshift variant is not clinically meaningful under this VCEP. Details ▾Hide ▴
Evidence considered
  • SpliceAI max delta: 0.00
  • BP4 splicing rule not intended for frameshift variants
Sources
spliceai ↗
BP7 N/ABP7 in the PALB2 VCEP applies to synonymous and deep intronic variants. NM_024675.4:c.509_510delGA is a frameshift variant. Details ▾Hide ▴
Evidence considered
  • VCEP BP7: applies to synonymous and deep intronic variants only
  • this is a frameshift

Statement

In silico

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

8 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

  • PALB2 mutations in BRCA1/2-mutation negative breast and ovarian cancer patients from Poland.
    No paper-specific finding is recorded.
    PMID 28279176 ↗
  • Identification of a novel truncating PALB2 mutation and analysis of its contribution to early-onset breast cancer in French-Canadian women.
    No paper-specific finding is recorded.
    PMID 18053174 ↗
  • A novel PALB2 truncating mutation in an Italian family with male breast cancer.
    No paper-specific finding is recorded.
    PMID 25529982 ↗
  • Rare, protein-truncating variants in ATM, CHEK2 and PALB2, but not XRCC2, are associated with increased breast cancer risks.
    No paper-specific finding is recorded.
    PMID 28779002 ↗
  • The Role of PALB2 in the DNA Damage Response and Cancer Predisposition.
    No paper-specific finding is recorded.
    PMID 28858227 ↗
  • Identification of a novel truncating mutation in PALB2 gene by a multigene sequencing panel for mutational screening of breast cancer risk-associated and related genes.
    No paper-specific finding is recorded.
    PMID 29484706 ↗
  • Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer.
    Reid S et al. · 2007
    No paper-specific finding is recorded.
    PMID 17200671 ↗
  • Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.
    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 30 / 1,614,006 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 49 Pathogenic · 1 pathogenic 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 ↗
ClinGen CSpec Captured ClinGen CSpec 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

This variant is present in gnomAD v4.1 (AF= 1.85873e-05; MAF= 0.00186%, 30/1614006 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 2.45759e-05; MAF= 0.00246%, 29/1180016 alleles, homozygotes = 0); grpmax FAF= 1.724e-05.

gnomAD v2.1

This variant is present in gnomAD v2.1 (AF= 3.5793e-05; MAF= 0.00358%, 9/251446 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.00016292; MAF= 0.01629%, 1/6138 alleles, homozygotes = 0); grpmax FAF= 3.419e-05.

ClinVar

This variant has been reported in ClinVar as Pathogenic (49 clinical laboratories) and as pathogenic (1 clinical laboratory). (ClinVarID = 126757)

In silico

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

Functional

OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.

Somatic

This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV108015612, n = 1 times).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.