NM_000051.4(ATM):c.1888G>A (p.Val630Met) AND Malignant tumor of breast

Clinical significance:Uncertain significance

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001356176.1

Allele description [Variation Report for NM_000051.4(ATM):c.1888G>A (p.Val630Met)]

NM_000051.4(ATM):c.1888G>A (p.Val630Met)

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.1888G>A (p.Val630Met)
HGVS:
  • NC_000011.10:g.108252902G>A
  • NG_009830.1:g.35071G>A
  • NM_000051.4:c.1888G>AMANE SELECT
  • NM_001351834.2:c.1888G>A
  • NP_000042.3:p.Val630Met
  • NP_000042.3:p.Val630Met
  • NP_001338763.1:p.Val630Met
  • LRG_135t1:c.1888G>A
  • LRG_135:g.35071G>A
  • LRG_135p1:p.Val630Met
  • NC_000011.9:g.108123629G>A
  • NM_000051.3:c.1888G>A
  • NM_000051.4:c.1888G>A
  • p.V630M
Protein change:
V630M
Links:
dbSNP: rs148191382
NCBI 1000 Genomes Browser:
rs148191382
Molecular consequence:
  • NM_000051.4:c.1888G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001351834.2:c.1888G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Malignant tumor of breast
Synonyms:
Breast cancer; Malignant breast neoplasm
Identifiers:
MONDO: MONDO:0007254; MedGen: C0006142

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001551267Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria providedUncertain significanceunknownclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownyes1not providednot providednot providednot providedclinical testing

Details of each submission

From Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001551267.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The ATM p.Val630Met variant was identified in 1 of 972 proband chromosomes (frequency: 0.001) from individuals or families with chronic lymphocytic leukemia (Jain 2016). The variant was also identified in dbSNP (ID: rs148191382) as "With Uncertain significance allele", and in ClinVar (classified as likely benign by Invitae; as uncertain significance by Ambry Genetics, GeneDx, Integrated Genetics/Laboratory Corporation of America) databases. The variant was not identified in GeneInsight-COGR, Cosmic, MutDB, or LOVD 3.0 databases. The variant was identified in control databases in 24 of 245222 chromosomes (1 homozygous) at a frequency of 0.0001 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Other in 1 of 5462 chromosomes (freq: 0.0002), Latino in 15 of 33478 chromosomes (freq: 0.0004), European in 6 of 111122 chromosomes (freq: 0.00005), East Asian in 1 of 17216 chromosomes (freq: 0.00006), and South Asian in 1 of 30672 chromosomes (freq: 0.00003), while the variant was not observed in the African, Ashkenazi Jewish, and Finnish populations. The p.Val630 residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Dec 4, 2021

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