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NM_000051.4(ATM):c.7914G>T (p.Trp2638Cys) AND Hereditary cancer-predisposing syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jun 27, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000569832.12

Allele description [Variation Report for NM_000051.4(ATM):c.7914G>T (p.Trp2638Cys)]

NM_000051.4(ATM):c.7914G>T (p.Trp2638Cys)

Genes:
ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]
C11orf65:chromosome 11 open reading frame 65 [Gene - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q22.3
Genomic location:
Preferred name:
NM_000051.4(ATM):c.7914G>T (p.Trp2638Cys)
HGVS:
  • NC_000011.10:g.108332887G>T
  • NG_009830.1:g.115056G>T
  • NG_054724.1:g.141946C>A
  • NM_000051.4:c.7914G>TMANE SELECT
  • NM_001330368.2:c.641-23816C>A
  • NM_001351110.2:c.*38+2333C>A
  • NM_001351834.2:c.7914G>T
  • NP_000042.3:p.Trp2638Cys
  • NP_000042.3:p.Trp2638Cys
  • NP_001338763.1:p.Trp2638Cys
  • LRG_135t1:c.7914G>T
  • LRG_135:g.115056G>T
  • LRG_135p1:p.Trp2638Cys
  • NC_000011.9:g.108203614G>T
  • NM_000051.3:c.7914G>T
Protein change:
W2638C
Links:
dbSNP: rs758843096
NCBI 1000 Genomes Browser:
rs758843096
Molecular consequence:
  • NM_001330368.2:c.641-23816C>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001351110.2:c.*38+2333C>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000051.4:c.7914G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351834.2:c.7914G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000668027Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Jun 27, 2023) 		germlineclinical testing

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From Ambry Genetics, SCV000668027.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The c.7914G>T variant (also known as p.W2638C), located in coding exon 52 of the ATM gene, results from a G to T substitution at nucleotide position 7914. The tryptophan at codon 2638 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may weaken the native splice donor site and may result in the creation or strengthening of a novel splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 10, 2024