NM_000051.4(ATM):c.172G>T (p.Asp58Tyr) AND Familial cancer of breast

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 15, 2022
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:: RCV002265695.1

Allele description [Variation Report for NM_000051.4(ATM):c.172G>T (p.Asp58Tyr)]

NM_000051.4(ATM):c.172G>T (p.Asp58Tyr)

Gene:

ATM:ATM serine/threonine kinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q22.3

Genomic location:

Preferred name:

NM_000051.4(ATM):c.172G>T (p.Asp58Tyr)

HGVS:

NC_000011.10:g.108227875G>T
NG_009830.1:g.10044G>T
NM_000051.4:c.172G>TMANE SELECT
NM_001351834.2:c.172G>T
NM_001351835.2:c.172G>T
NM_001351836.2:c.172G>T
NP_000042.3:p.Asp58Tyr
NP_000042.3:p.Asp58Tyr
NP_001338763.1:p.Asp58Tyr
NP_001338764.1:p.Asp58Tyr
NP_001338765.1:p.Asp58Tyr
LRG_135t1:c.172G>T
LRG_135:g.10044G>T
LRG_135p1:p.Asp58Tyr
NC_000011.9:g.108098602G>T
NM_000051.3:c.172G>T

Protein change:

D58Y

Links:

dbSNP: rs876660661

NCBI 1000 Genomes Browser:

rs876660661

Molecular consequence:

NM_000051.4:c.172G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351834.2:c.172G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351835.2:c.172G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001351836.2:c.172G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial cancer of breast
Synonyms:: Breast cancer, familial; Hereditary breast cancer
Identifiers:: MONDO: MONDO:0016419; MedGen: C0346153; OMIM: 114480

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002548544	Department of Molecular Diagnostics, Institute of Oncology Ljubljana	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 15, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 35806449, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002548544

Department of Molecular Diagnostics, Institute of Oncology Ljubljana

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 15, 2022)

germline

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Identification of Spliceogenic Variants beyond Canonical GT-AG Splice Sites in Hereditary Cancer Genes.

Dragoš VŠ, Strojnik K, Klančar G, Škerl P, Stegel V, Blatnik A, Banjac M, Krajc M, Novaković S.

Int J Mol Sci. 2022 Jul 4;23(13). doi:pii: 7446. 10.3390/ijms23137446.

PubMed [citation]

PMID:: 35806449
PMCID:: PMC9267136

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Department of Molecular Diagnostics, Institute of Oncology Ljubljana, SCV002548544.1

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

Description

ATM:c.172G>T variant is absent from the large population studies (GnomAd). The variant is predicted to create a de novo donor splice site in exon 3 by in silico splicing tools. Functional RNA study has shown that the variant causes an incomplete splicing aberration that causes the creation of a premature stop codon (PMID: 35806449). Additionally, the variant also produced a slightly expressed full-length transcript. Therefore the variant was classified as variant of uncertain significance (ACMG/AMP: PM2-supp, PP3, PS3-m)

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

Last Updated: Sep 29, 2024

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