NM_007294.4(BRCA1):c.4657T>A (p.Leu1553Met) AND Hereditary breast and ovarian cancer syndrome

Clinical significance:Uncertain significance (Last evaluated: Feb 29, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001364498.1

Allele description [Variation Report for NM_007294.4(BRCA1):c.4657T>A (p.Leu1553Met)]

NM_007294.4(BRCA1):c.4657T>A (p.Leu1553Met)

Gene:
BRCA1:BRCA1 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.31
Genomic location:
Preferred name:
NM_007294.4(BRCA1):c.4657T>A (p.Leu1553Met)
Other names:
p.L1553M:TTG>ATG
HGVS:
  • NC_000017.11:g.43074349A>T
  • NG_005905.2:g.143635T>A
  • NM_007294.3:c.4657T>A
  • NM_007294.4:c.4657T>AMANE SELECT
  • NM_007297.4:c.4516T>A
  • NM_007298.3:c.1345T>A
  • NM_007299.4:c.1345T>A
  • NM_007300.4:c.4720T>A
  • NP_009225.1:p.Leu1553Met
  • NP_009225.1:p.Leu1553Met
  • NP_009228.2:p.Leu1506Met
  • NP_009229.2:p.Leu449Met
  • NP_009230.2:p.Leu449Met
  • NP_009231.2:p.Leu1574Met
  • LRG_292t1:c.4657T>A
  • LRG_292:g.143635T>A
  • LRG_292p1:p.Leu1553Met
  • NC_000017.10:g.41226366A>T
  • NM_007294.4:c.4657T>A
  • NR_027676.2:n.4834T>A
  • U14680.1:n.4776T>A
  • p.L1553M
Nucleotide change:
4776T>A
Protein change:
L1506M
Links:
dbSNP: rs80357431
NCBI 1000 Genomes Browser:
rs80357431
Molecular consequence:
  • NM_007294.3:c.4657T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007294.4:c.4657T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007297.4:c.4516T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007298.3:c.1345T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007299.4:c.1345T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007300.4:c.4720T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_027676.2:n.4834T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Hereditary breast and ovarian cancer syndrome (HBOC)
Synonyms:
Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC)
Identifiers:
MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145; OMIM: PS604370

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001560651Invitaecriteria provided, single submitter
Uncertain significance
(Feb 29, 2020)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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

Citations

PubMed

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001560651.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces leucine with methionine at codon 1553 of the BRCA1 protein (p.Leu1553Met). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and methionine. This variant is present in population databases (rs80357431, ExAC 0.001%). This variant has not been reported in the literature in individuals with BRCA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 55254). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0. The methionine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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

Last Updated: Sep 18, 2021

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