NM_000051.4(ATM):c.7871G>C (p.Cys2624Ser) AND Ataxia-telangiectasia syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 16, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000696595.16

Allele description [Variation Report for NM_000051.4(ATM):c.7871G>C (p.Cys2624Ser)]

NM_000051.4(ATM):c.7871G>C (p.Cys2624Ser)

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.7871G>C (p.Cys2624Ser)

Other names:

p.Cys2624Ser

HGVS:

NC_000011.10:g.108332844G>C
NG_009830.1:g.115013G>C
NG_054724.1:g.141989C>G
NM_000051.4:c.7871G>CMANE SELECT
NM_001330368.2:c.641-23773C>G
NM_001351110.2:c.*38+2376C>G
NM_001351834.2:c.7871G>C
NP_000042.3:p.Cys2624Ser
NP_000042.3:p.Cys2624Ser
NP_001338763.1:p.Cys2624Ser
LRG_135t1:c.7871G>C
LRG_135:g.115013G>C
LRG_135p1:p.Cys2624Ser
NC_000011.9:g.108203571G>C
NM_000051.3:c.7871G>C

Protein change:

C2624S

Links:

dbSNP: rs759392666

NCBI 1000 Genomes Browser:

rs759392666

Molecular consequence:

NM_001330368.2:c.641-23773C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001351110.2:c.*38+2376C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000051.4:c.7871G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.7871G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Ataxia-telangiectasia syndrome (AT)
Synonyms:: Louis-Bar syndrome; Cerebello-oculocutaneous telangiectasia; Immunodeficiency with ataxia telangiectasia; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008840; MedGen: C0004135; Orphanet: 100; OMIM: 208900

Recent activity

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transcription elongation factor SPT5 isoform X2 [Rattus norvegicus]
transcription elongation factor SPT5 isoform X2 [Rattus norvegicus]
gi|1958645427|ref|XP_038967497.1|

Protein
transcription elongation factor SPT5 isoform X1 [Rattus norvegicus]
transcription elongation factor SPT5 isoform X1 [Rattus norvegicus]
gi|2678866179|ref|XP_063117577.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000825160	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 16, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 35264596, 28492532
SCV000838599	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Uncertain significance (Jul 2, 2018)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000825160

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 16, 2024)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV000838599

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2017)

Uncertain significance
(Jul 2, 2018)

unknown

clinical testing

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Detection of germline variants in Brazilian breast cancer patients using multigene panel testing.

Guindalini RSC, Viana DV, Kitajima JPFW, Rocha VM, López RVM, Zheng Y, Freitas É, Monteiro FPM, Valim A, Schlesinger D, Kok F, Olopade OI, Folgueira MAAK.

Sci Rep. 2022 Mar 9;12(1):4190. doi: 10.1038/s41598-022-07383-1.

PubMed [citation]

PMID:: 35264596
PMCID:: PMC8907244

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000825160.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 2624 of the ATM protein (p.Cys2624Ser). This variant is present in population databases (rs759392666, gnomAD 0.003%). This missense change has been observed in individual(s) with breast cancer (PMID: 35264596). ClinVar contains an entry for this variant (Variation ID: 574618). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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

From Mendelics, SCV000838599.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

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

Last Updated: Nov 10, 2024

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