NM_000051.4(ATM):c.7865C>T (p.Ala2622Val) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 11, 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:: RCV001026887.12

Allele description [Variation Report for NM_000051.4(ATM):c.7865C>T (p.Ala2622Val)]

NM_000051.4(ATM):c.7865C>T (p.Ala2622Val)

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.7865C>T (p.Ala2622Val)

HGVS:

NC_000011.10:g.108332838C>T
NG_009830.1:g.115007C>T
NG_054724.1:g.141995G>A
NM_000051.4:c.7865C>TMANE SELECT
NM_001330368.2:c.641-23767G>A
NM_001351110.2:c.*38+2382G>A
NM_001351834.2:c.7865C>T
NP_000042.3:p.Ala2622Val
NP_000042.3:p.Ala2622Val
NP_001338763.1:p.Ala2622Val
LRG_135t1:c.7865C>T
LRG_135:g.115007C>T
LRG_135p1:p.Ala2622Val
NC_000011.9:g.108203565C>T
NM_000051.3:c.7865C>T

Protein change:

A2622V

Links:

dbSNP: rs766351395

NCBI 1000 Genomes Browser:

rs766351395

Molecular consequence:

NM_001330368.2:c.641-23767G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*38+2382G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.7865C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.7865C>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

Recent activity

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PREDICTED: Rattus norvegicus potassium voltage-gated channel subfamily B member ...
PREDICTED: Rattus norvegicus potassium voltage-gated channel subfamily B member 1 (Kcnb1), transcript variant X1, misc_RNA
gi|2678927468|ref|XR_010064569.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001189357	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jan 11, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 10330348, 14695534, 16411093, 17389389, 20945614, 9892178 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001189357

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jan 11, 2023)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Splicing defects in the ataxia-telangiectasia gene, ATM: underlying mutations and consequences.

Teraoka SN, Telatar M, Becker-Catania S, Liang T, Onengüt S, Tolun A, Chessa L, Sanal O, Bernatowska E, Gatti RA, Concannon P.

Am J Hum Genet. 1999 Jun;64(6):1617-31.

PubMed [citation]

PMID:: 10330348
PMCID:: PMC1377904

Nonclassical splicing mutations in the coding and noncoding regions of the ATM Gene: maximum entropy estimates of splice junction strengths.

Eng L, Coutinho G, Nahas S, Yeo G, Tanouye R, Babaei M, Dörk T, Burge C, Gatti RA.

Hum Mutat. 2004 Jan;23(1):67-76.

PubMed [citation]

PMID:: 14695534

See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV001189357.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

The c.7865C>T pathogenic mutation (also known as p.A2622V), located in coding exon 52 of the ATM gene, results from a C to T substitution at nucleotide position 7865. The alanine at codon 2622 is replaced by valine, an amino acid with similar properties. This alteration has been detected in a homozygous state in multiple individuals with Ataxia Telangiectasia (Teraoka SN et al. Am. J. Hum. Genet., 1999 Jun;64:1617-31; Eng L et al. Hum. Mutat., 2004 Jan;23:67-76; Heinrich T et al. Eur. J. Pediatr., 2006 Apr;165:250-7; Aghamohammadi A et al. J Investig Allergol Clin Immunol, 2010;20:442-5). In silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice donor site. RNA analyses have shown that this alteration creates a new splice donor site, resulting in a deletion of 64 nucleotides from exon 52 and an out of frame transcript (Teraoka SN et al. Am. J. Hum. Genet., 1999 Jun;64:1617-31, Eng L et al. Hum. Mutat., 2004 Jan;23:67-76, Du L et al. Proc. Natl. Acad. Sci. U.S.A., 2007 Apr;104:6007-12, Ambry internal data). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 8, 2024

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