U.S. flag

An official website of the United States government

NM_000051.4(ATM):c.901+1G>C AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 23, 2024
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:
RCV001018639.4

Allele description [Variation Report for NM_000051.4(ATM):c.901+1G>C]

NM_000051.4(ATM):c.901+1G>C

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.901+1G>C
HGVS:
  • NC_000011.10:g.108245027G>C
  • NG_009830.1:g.27196G>C
  • NM_000051.4:c.901+1G>CMANE SELECT
  • NM_001351834.2:c.901+1G>C
  • LRG_135t1:c.901+1G>C
  • LRG_135:g.27196G>C
  • NC_000011.9:g.108115754G>C
  • NM_000051.3:c.901+1G>C
Links:
dbSNP: rs748840480
NCBI 1000 Genomes Browser:
rs748840480
Molecular consequence:
  • NM_000051.4:c.901+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001351834.2:c.901+1G>C - splice donor variant - [Sequence Ontology: SO:0001575]

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

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001179900Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(May 23, 2024) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From Ambry Genetics, SCV001179900.5

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

Description

The c.901+1G>C intronic pathogenic mutation results from a G to C substitution one nucleotide after coding exon 6 of the ATM gene. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In silico splice site analysis predicts that this alteration will weaken the native splice donor site. RNA studies have demonstrated that this alteration results in abnormal splicing in the set of samples tested (Ambry internal data). Another alteration impacting the same donor site (c.901+1G>A) has been detected in conjunction with a truncating ATM mutation in a Hispanic-American ataxia-telangiectasia family (Mitui M et al. Hum. Mutat. 2003 Jul;22(1):43-50), and in a male breast cancer patient and an ovarian cancer patient (Pritzlaff M et al. Breast Cancer Res. Treat. 2017 02;161(3):575-586; Crawford B et al. Breast Cancer Res. Treat. 2017 Jun;163(2):383-390). Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Sep 8, 2024