Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000051.3(ATM):c.5544T>C (p.Asp1848=)

Curation Version - 1.1
Curation History
JSON LD for Version 1.1

CA190548

184944 (ClinVar)

Gene: ATM

Condition: hereditary breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 8bb6d6b8-0127-4357-805c-ebd934c74e8c

Approved on: 2022-03-09

Published on: 2022-07-11

HGVS expressions

NM_000051.3:c.5544T>C

NM_000051.3(ATM):c.5544T>C (p.Asp1848=)

NC_000011.10:g.108304722T>C

CM000673.2:g.108304722T>C

NC_000011.9:g.108175449T>C

CM000673.1:g.108175449T>C

NC_000011.8:g.107680659T>C

NG_009830.1:g.86891T>C

ENST00000278616.9:c.5544T>C

ENST00000683174.1:n.7028T>C

ENST00000683524.1:n.768T>C

ENST00000684152.1:n.1258T>C

ENST00000527805.6:c.*608T>C

ENST00000675595.1:c.*608T>C

ENST00000675843.1:c.5544T>C

ENST00000278616.8:c.5544T>C

ENST00000452508.6:c.5544T>C

ENST00000524792.5:n.1759T>C

ENST00000529588.5:n.56T>C

ENST00000533690.5:n.948T>C

NM_001351834.1:c.5544T>C

NM_001351834.2:c.5544T>C

NM_000051.4:c.5544T>C

NM_000051.4(ATM):c.5544T>C (p.Asp1848=)

Likely Benign

BP4 BP7

PM2 BA1 BS1

Evidence Links 0

Expert Panel

Hereditary Breast, Ovarian and Pancreatic Cancer VCEP

Criteria Specification Information

Criteria Specification: ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ATM Version 1.1

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hereditary Breast, Ovarian and Pancreatic Cancer VCEP

The ATM c.5544T>C (p.Asp1848=) variant is not predicted to impact splicing in multiple RNA in silico tools (BP4). This variant creates a synonymous change (BP7). In summary, this variant meets criteria to be classified as likely benign based on the ACMG/AMP criteria applied as specified by the HBOP Variant Curation Expert Panel.

BP4

In silico splicing predictors (SpliceAI: AL 0.06 +14bp, AG 0.01 -47 bp, not significant, MaxEntScan: WT=2.59 Variant= 2.24) predict that this alteration will not have a significant impact on splicing (BP4).

BP7

This variant creates a synonymous change (BP7).

PM2

This variant has an allele frequency of 0.006% in gnomAD v2.1.1 (African/African-American sub-population) which is greater than the PM2 threshold but below the BS1 threshold set for this gene.

BA1

BS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Curation History

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