GATA2c.474C>TLikely benign

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Variant interpretation report

GATA2 c.474C>T, p.(Ser158=)

NM_001145661.1:c.474C>T NP_001139133.1:p.(Ser158=) 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 GATA2

No gene-level summary was recorded for this case.

Key facts

Evidence used: 3 supporting (benign)
Expert rules: Not recorded
Other laboratories (ClinVar): 2 Likely benign
Pipeline record: 4 Aug 2026 · version 7.0.5

Evidence considered

View criteria

Applied evidence criteria

BP4 (supporting): Computational evidence suggests no impact on the gene product: SpliceAI predicts no splicing impact (max delta score = 0.00), the variant is synonymous with no amino acid change, and no in silico tool predicts a deleterious effect.
BP6 (supporting): Two clinical testing laboratories (Ambry Genetics and Labcorp/Invitae) have classified this variant as Likely benign in ClinVar (VariationID 1081290). Although review status is 'criteria provided, single submitter' and not 3-star expert panel, two independent clinical laboratory submissions provide reproducible benign evidence.
BP7 (supporting): Synonymous variant (p.Ser158=) for which SpliceAI predicts no impact on splicing (max delta score = 0.00; no predicted acceptor gain, acceptor loss, donor gain, or donor loss). The nucleotide position is not predicted to affect the splice consensus sequence or create a novel splice site.

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 Not recorded. 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: 3

Pathogenic criteria applied · 0

No pathogenic criterion marked as applied in the recorded assessment.

Benign criteria applied · 3

BP4Supporting

BP4 · supporting

Computational evidence suggests no impact on the gene product: SpliceAI predicts no splicing impact (max delta score = 0.00), the variant is synonymous with no amino acid change, and no in silico tool predicts a deleterious effect.

BP6Supporting

BP6 · supporting

Two clinical testing laboratories (Ambry Genetics and Labcorp/Invitae) have classified this variant as Likely benign in ClinVar (VariationID 1081290). Although review status is 'criteria provided, single submitter' and not 3-star expert panel, two independent clinical laboratory submissions provide reproducible benign evidence.

BP7Supporting

BP7 · supporting

Synonymous variant (p.Ser158=) for which SpliceAI predicts no impact on splicing (max delta score = 0.00; no predicted acceptor gain, acceptor loss, donor gain, or donor loss). The nucleotide position is not predicted to affect the splice consensus sequence or create a novel splice site.

Recorded classification: Likely benign

gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BP4 supporting benign, BP6 supporting benign, BP7 supporting benign; combination = 3 supporting benign, which 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

Not recorded

gnomAD v4.1 allele counts were not recorded for this variant.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

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.

Applied · BP4, BP7 → SpliceAI ↗

ClinVar submissions

2 reported laboratory submissions

2 Likely benign. ClinVar API review status: criteria provided, multiple submitters, no conflicts.

Applied · BP6 → ClinVar ↗

Functional evidence

Statement recorded

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

No listed criterion applied 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 Not recorded, with the data and sources behind each one.

29 criteria with recorded statuses: 3 met · 18 not met · 0 not assessed · 8 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic

PVS1 PS1 PS2 PS3 PS4 PM1 PM2 PM3 PM4 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_001145661.1:c.474C>T (p.Ser158=) is a synonymous variant in GATA2 with no predicted impact on splicing (SpliceAI max delta = 0.00).

This variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada population databases.

Two clinical testing laboratories (Ambry Genetics and Labcorp/Invitae) have independently classified this variant as Likely benign in ClinVar (VariationID 1081290).

No published study reports this exact variant; reviewed literature covers GATA2 loss-of-function disease mechanism at gene level only.

BP4 is met: computational evidence (SpliceAI, no amino acid change) suggests no impact on the gene product.

BP6 is met: the variant has been reported as Likely benign by two independent clinical laboratories.

BP7 is met: this is a synonymous variant for which splicing prediction algorithms predict no impact on the splice consensus sequence nor the creation of a new splice site.

Three supporting benign criteria are met (BP4, BP6, BP7). Under generic ACMG/AMP 2015 combination rules, two supporting benign criteria are sufficient for a Likely Benign classification.

Met · 3

BP4 SupportingComputational evidence suggests no impact on the gene product: SpliceAI predicts no splicing impact (max delta score = 0.00), the variant is synonymous with no amino acid change, and no in silico tool predicts a deleterious effect. Details ▾Hide ▴

Evidence considered

SpliceAI max delta score = 0.00
no predicted impact on any splice site (acceptor gain
acceptor loss
donor gain
donor loss all null).
Synonymous variant (p.Ser158=) with no amino acid substitution.
No REVEL
BayesDel
or HCI prior scores suggesting deleteriousness.

Sources

spliceai ↗

BP6 SupportingTwo clinical testing laboratories (Ambry Genetics and Labcorp/Invitae) have classified this variant as Likely benign in ClinVar (VariationID 1081290). Although review status is 'criteria provided, single submitter' and not 3-star expert panel, two independent clinical laboratory submissions provide reproducible benign evidence. Details ▾Hide ▴

Evidence considered

ClinVar VariationID 1081290: Likely benign.
Two submissions: Ambry Genetics (SCV006531223) and Labcorp/Invitae (SCV001598983)
both Likely benign.
Both submissions are clinical testing
germline origin
no expert panel submissions.

Still missing

No expert panel review
individual submissions lack a detailed criteria breakdown.

Sources

clinvar ↗

BP7 SupportingSynonymous variant (p.Ser158=) for which SpliceAI predicts no impact on splicing (max delta score = 0.00; no predicted acceptor gain, acceptor loss, donor gain, or donor loss). The nucleotide position is not predicted to affect the splice consensus sequence or create a novel splice site. Details ▾Hide ▴

Evidence considered

Variant is synonymous: NP_001139133.1:p.(Ser158=).
SpliceAI max delta score = 0.00
all individual delta scores (acceptor gain
acceptor loss
donor gain
donor loss) are null.
No predicted creation or disruption of splice sites.

Still missing

Nucleotide-level conservation scores (PhyloP/GERP) not evaluated
conservation assumption based on zero SpliceAI score.

Sources

spliceai ↗

Not met · 18 · evaluated, threshold not reached

PS2 No de novo data available for this variant; PS2 requires a confirmed de novo occurrence with maternity and paternity confirmed. Details ▾Hide ▴

Still missing

No de novo testing or family studies identified for this variant.

PS3 No functional data identified for this variant. The variant is synonymous with no predicted impact on splicing (SpliceAI max delta = 0.00), and no experimental studies have tested this variant or a systematically characterized range that includes it. Details ▾Hide ▴

Evidence considered

SpliceAI predicts no significant splice impact (max delta score = 0.00).
No published functional studies identified for NM_001145661.1:c.474C>T
no saturation mutagenesis
tiling screen
or systematic truncation series spans this position.

Still missing

No functional characterization of this synonymous variant in any experimental system.

Sources

spliceai ↗

PS4 No case-control or enrichment data demonstrating a statistically significant association of this variant with disease. Details ▾Hide ▴

Still missing

No case-control studies or cohort data available for this variant.

PM1 Variant does not lie in a known critical functional domain hotspot; cancerhotspots.org does not identify this residue as statistically significant, and as a synonymous variant it does not alter any residue within a characterized functional domain. Details ▾Hide ▴

Evidence considered

Not located in a statistically significant hotspot on cancerhotspots.org.
Synonymous change (p.Ser158=) cannot disrupt a critical functional domain at the protein level.

PM2 Variant is absent from gnomAD v2.1 and v4.1; however, this is a synonymous variant with no predicted functional impact (SpliceAI max delta = 0.00, no REVEL/BayesDel scores). Absence from population databases in the absence of any other pathogenic evidence does not constitute meaningful evidence of pathogenicity for a synonymous variant. Details ▾Hide ▴

Evidence considered

Absent from gnomAD v2.1
v4.1
and gnomAD-Canada.
Synonymous variant with no predicted splicing or functional impact.

Still missing

gnomAD allele count and allele number are null
coverage at this position could not be confirmed.

Sources

gnomad_v2 ↗gnomad_v4 ↗gnomad_canada ↗

PM6 No de novo data available; PM6 requires a presumed de novo occurrence without confirmation of maternity and paternity. Details ▾Hide ▴

Still missing

No de novo testing identified for this variant.

PP1 No segregation data available for this variant. Details ▾Hide ▴

Still missing

No family studies or segregation analysis identified.

PP3 Computational evidence supports a benign, not deleterious, interpretation: SpliceAI max delta = 0.00 (no splicing impact); no REVEL, BayesDel, or HCI prior scores are available. Details ▾Hide ▴

Evidence considered

SpliceAI max delta score = 0.00
no predicted splice acceptor gain
acceptor loss
donor gain
or donor loss.
REVEL score not available for this variant.
BayesDel score not available for this variant.
HCI prior not available for GATA2.

Sources

spliceai ↗

PP4 No patient phenotype or clinical data available for this variant. Details ▾Hide ▴

Still missing

No proband phenotype or clinical data provided.

PP5 ClinVar classification is Likely benign (2 clinical laboratories, single submitter review status), not pathogenic; PP5 requires a pathogenic assertion from a reputable source. Details ▾Hide ▴

Evidence considered

ClinVar VariationID 1081290: Likely benign
review status 'criteria provided
single submitter'.
Two clinical laboratory submissions (Ambry Genetics
Labcorp/Invitae)
both Likely benign
no expert panel submissions.

Sources

clinvar ↗

BA1 Variant is absent from gnomAD; allele frequency is 0%, which does not exceed the BA1 threshold of >1%. Details ▾Hide ▴

Evidence considered

Absent from gnomAD v2.1 and v4.1 (AF = 0%).

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS1 Variant is absent from gnomAD; allele frequency is 0%, which does not exceed the BS1 threshold of >0.3%. Details ▾Hide ▴

Evidence considered

Absent from gnomAD v2.1 and v4.1 (AF = 0%).

Sources

gnomad_v2 ↗gnomad_v4 ↗

BS2 No data on observation of this variant in healthy adults for a fully penetrant disorder. Details ▾Hide ▴

Still missing

No population-specific healthy adult screening data available.

BS3 No functional studies demonstrating no deleterious effect of this variant. The synonymous nature and zero SpliceAI score are consistent with a benign effect, but these are computational predictions, not experimental functional data as required by BS3. Details ▾Hide ▴

Evidence considered

SpliceAI max delta = 0.00 suggests no splicing impact
but this is in silico prediction
not experimental functional evidence.

Still missing

No experimental functional studies (e.g.
splicing assays
protein function) performed for this variant.

Sources

spliceai ↗

BS4 No segregation data available demonstrating lack of cosegregation with disease. Details ▾Hide ▴

Still missing

No family studies demonstrating absence of segregation with disease.

BP2 No evidence of this variant observed in trans with a pathogenic variant in GATA2. Details ▾Hide ▴

Still missing

No phase data or trans observation data available.

BP5 No evidence of an alternative molecular basis for disease in this case. Details ▾Hide ▴

Still missing

No data on alternative molecular diagnoses available.

PS5 ClinVar reports Likely benign, not pathogenic; PS5 requires a pathogenic assertion from a reputable source. Details ▾Hide ▴

Evidence considered

ClinVar classification is Likely benign (2 clinical laboratories)
not pathogenic.

Sources

clinvar ↗

Not applicable · 8· recorded as not applicable Show reasons ▾Hide reasons ▴

PVS1 N/ASynonymous variant (p.Ser158=); does not fall into null-variant buckets (nonsense, frameshift, or canonical ±1,2 splice consensus). Details ▾Hide ▴

Evidence considered

NM_001145661.1:c.474C>T is a synonymous substitution resulting in no amino acid change (NP_001139133.1:p.(Ser158=)).
Variant bucket is 'other'
generic PVS1 framework (PMC6185798) does not apply.

Sources

pvs1_variant_assessmentpvs1_gene_context

PS1 N/ASynonymous variant does not produce a missense change; PS1 requires a different nucleotide change resulting in the same amino acid substitution as a known pathogenic variant. Details ▾Hide ▴

Evidence considered

Variant is synonymous (p.Ser158=)
no amino acid substitution to compare.

PM3 N/APM3 (recessive/compound heterozygosity) is not applicable: GATA2 deficiency is autosomal dominant and no trans configuration evidence is assessed for this synonymous variant. Details ▾Hide ▴

No further detail was recorded.

PM4 N/APM4 requires an in-frame insertion/deletion altering protein length; this is a synonymous substitution with no protein length change. Details ▾Hide ▴

No further detail was recorded.

PM5 N/ASynonymous variant (p.Ser158=); PM5 requires a different missense change at the same residue with a known pathogenic classification. No amino acid change occurs. Details ▾Hide ▴

Evidence considered

Variant is synonymous
no missense comparator is possible.
PM5 candidate harvest found 0 same-residue candidates (pm5_candidates.json).

Sources

pm5_candidates

PP2 N/APP2 applies to missense variants in genes with a low rate of benign missense variation; this is a synonymous variant, not a missense change. Details ▾Hide ▴

Evidence considered

Variant is synonymous (p.Ser158=)
not missense.

BP1 N/ABP1 is specific to missense variants in genes where primarily truncating variants cause disease; this is a synonymous variant, not a missense change. Details ▾Hide ▴

Evidence considered

Variant is synonymous (p.Ser158=)
not missense.

BP3 N/ABP3 applies to variants in repeat regions or involving repeat length; this is a single-nucleotide substitution outside a repeat region. Details ▾Hide ▴

No further detail was recorded.

Identifiers

Gene: GATA2
Transcript: NM_001145661.1
Coding (HGVS c.): NM_001145661.1:c.474C>T
Protein (HGVS p.): NP_001139133.1:p.(Ser158=)
GRCh38: chr3:128486124 G>A
GRCh37: chr3:128204967 G>A
ClinVar: 1081290

Gene diagram

Every interpreted variant in GATA2, mapped onto the exon structure of NM_001145661.1. Select a row to find it on the plot.

GATA2NM_001145661.1

Fetching transcript structure from UCSC…

Exons

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Transcript span

—

Strand

—

Variants mapped

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Source

UCSC ncbiRefSeqCurated

All variants in GATA2 — Select a row to find it on the plot; use the link to open its page.

	Protein	Location	Classification	Link

gnomAD v4.1 Allele count data not recorded

gnomAD v2.1 Allele count data not recorded

gnomAD-Canada v1.0 Allele count data not recorded

Statements

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

SpliceAI and Pangolin

Pangolin splice lossmagnitude shown

-0.030

Pangolin splice gain

0.250

Other predictors

REVEL: Not available
BayesDel: Not available

How the predictions were used

Evidence considered

SpliceAI max delta score = 0.00
no predicted impact on any splice site (acceptor gain
acceptor loss
donor gain
donor loss all null).
Synonymous variant (p.Ser158=) with no amino acid substitution.
No REVEL
BayesDel
or HCI prior scores suggesting deleteriousness.

Sources

spliceai ↗

Evidence considered

Variant is synonymous: NP_001139133.1:p.(Ser158=).
SpliceAI max delta score = 0.00
all individual delta scores (acceptor gain
acceptor loss
donor gain
donor loss) are null.
No predicted creation or disruption of splice sites.

Still missing

Nucleotide-level conservation scores (PhyloP/GERP) not evaluated
conservation assumption based on zero SpliceAI score.

Sources

spliceai ↗

Evidence considered

SpliceAI max delta score = 0.00
no predicted splice acceptor gain
acceptor loss
donor gain
or donor loss.
REVEL score not available for this variant.
BayesDel score not available for this variant.
HCI prior not available for GATA2.

Sources

spliceai ↗

Statement

In silico

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

6 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

ACMG position statement on prenatal/preconception expanded carrier screening.

ACMG position statement on prenatal/preconception expanded carrier screening. Discusses criteria for inclusion of disorders on carrier screening panels. GATA2 and NM_001145661.1:c.474C>T were not identified in this paper.
Does not name this variant
PMID 23619275 ↗
Whole-genome sequencing in newborn screening? A statement on the continued importance of targeted approaches in newborn screening programmes.

Howard HC et al. · 2015

Statement on the role of whole-genome sequencing in newborn screening programs. Discusses NGS technologies and their application to population screening. GATA2 and NM_001145661.1:c.474C>T were not identified.
Does not name this variant
PMID 25626707 ↗
Specific guidelines for assessing and improving the methodological quality of economic evaluations of newborn screening.

Langer A et al. · 2012

Guidelines for assessing methodological quality of economic evaluations of newborn screening. GATA2 and NM_001145661.1:c.474C>T were not identified.
Does not name this variant
PMID 22947299 ↗
Including the initial newborn screening bloodspot collection device serial number on birth certificates: basis and recommendations from the Secretary of Health and Human Services' Advisory Committee on Heritable Disorders in Newborns and Children.

Therrell BL et al. · 2013

Recommendations on including newborn screening bloodspot collection device serial numbers on birth certificates. GATA2 and NM_001145661.1:c.474C>T were not identified.
Does not name this variant
PMID 23037933 ↗
Offering prenatal diagnostic tests: European guidelines for clinical practice [corrected].

Skirton H et al. · 2014

European guidelines for offering prenatal diagnostic tests in clinical practice. GATA2 and NM_001145661.1:c.474C>T were not identified.
Does not name this variant
PMID 24022298 ↗
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Provides a systematic framework for variant interpretation. GATA2 and NM_001145661.1:c.474C>T were not identified.
Does not name this variant
PMID 28492532 ↗

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

gnomAD v4.1 Captured gnomAD v4.1 source record Open source ↗

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

SpliceAI Lookup Recorded maximum delta 0.000 Open source ↗

ClinVar 2 Likely 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

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

ClinVar

This variant has been reported in ClinVar as Likely benign (2 clinical laboratories). (ClinVarID = 1081290)

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.