Variant: NM_000051.3(ATM):c.2639-17G>T

CA163513

140763 (ClinVar)

Gene: ATM

Condition: hereditary breast cancer

Inheritance Mode: Autosomal dominant inheritance

UUID: 12e51ac3-f131-4b31-8659-d7e9bb1ed185

Approved on: 2022-03-09

Published on: 2022-07-11

HGVS expressions

NM_000051.3:c.2639-17G>T
NM_000051.3(ATM):c.2639-17G>T
NC_000011.10:g.108268393G>T
CM000673.2:g.108268393G>T
NC_000011.9:g.108139120G>T
CM000673.1:g.108139120G>T
NC_000011.8:g.107644330G>T
NG_009830.1:g.50562G>T
ENST00000278616.9:c.2639-17G>T
ENST00000682516.1:n.2772+1051G>T
ENST00000683174.1:n.2789-17G>T
ENST00000684037.1:c.*1573+1051G>T
ENST00000527805.6:c.2639-17G>T
ENST00000675595.1:c.2474-17G>T
ENST00000675843.1:c.2639-17G>T
ENST00000278616.8:c.2639-17G>T
ENST00000452508.6:c.2639-17G>T
ENST00000527805.5:c.2639-17G>T
NM_001351834.1:c.2639-17G>T
NM_001351834.2:c.2639-17G>T
NM_000051.4:c.2639-17G>T
NM_000051.4(ATM):c.2639-17G>T

Benign

• Met criteria codes: BP2_Strong BP4 BA1

• Not Met criteria codes: PM2 BS1 BP7 PP3

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

Evidence submitted by expert panel

Hereditary Breast, Ovarian and Pancreatic Cancer VCEP

The ATM c.2639-17G>T variant has a gnomAD v2.1.1 filtering allele frequency of 6.505% (African/African-American; exomes) which exceeds the ATM BA1 threshold of 0.50% (BA1). This variant has been observed in a homozygous state in multiple individuals without biallelic disease (BP2_Strong; GTR Lab ID: 61756). In silico splicing predictors (SpliceAI: AL 0.00/DL 0.00/AG 0.01/DG 0.00; MaxEntScan: +1.92% (wild type = 9.90, variant = 10.09)) find that this variant is unlikely to affect splicing (BP4). In summary, this variant meets criteria to be classified as benign based on the ACMG/AMP criteria applied as specified by the HBOP Variant Curation Expert Panel.

Met criteria codes

• BP2_Strong: This variant has been observed in a homozygous state in multiple individuals without biallelic disease (BP2_Strong; GTR Lab ID: 61756).
• BP4: In silico splicing predictors (SpliceAI: AL 0.00/DL 0.00/AG 0.01/DG 0.00; MaxEntScan: +1.92% (wild type = 9.90, variant = 10.09)) find that this variant is unlikely to affect splicing (BP4).
• BA1: GnomAD v2.1.1 FAF 6.505% (African/African-American; exomes) exceeds ATM BA1 threshold of 0.50%.

Not Met criteria codes

• PM2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BS1: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
• BP7: This variant is not considered deep intronic (beyond +20 or beyond -40).
• PP3: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline