rs773184912
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000059.4(BRCA2):c.335G>A(p.Ser112Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000059.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRCA2 | NM_000059.4 | c.335G>A | p.Ser112Asn | missense_variant | 4/27 | ENST00000380152.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRCA2 | ENST00000380152.8 | c.335G>A | p.Ser112Asn | missense_variant | 4/27 | 5 | NM_000059.4 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250856Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135636
GnomAD4 exome AF: 6.93e-7 AC: 1AN: 1442010Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1AN XY: 718626
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 04, 2023 | The p.S112N variant (also known as c.335G>A), located in coding exon 3 of the BRCA2 gene, results from a G to A substitution at nucleotide position 335. The serine at codon 112 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Hereditary breast ovarian cancer syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 18, 2021 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The asparagine 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. This variant has not been reported in the literature in individuals with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 409529). This variant is present in population databases (rs773184912, ExAC 0.002%). This sequence change replaces serine with asparagine at codon 112 of the BRCA2 protein (p.Ser112Asn). The serine residue is moderately conserved and there is a small physicochemical difference between serine and asparagine. - |
Breast-ovarian cancer, familial, susceptibility to, 2 Benign:1
Likely benign, no assertion criteria provided | clinical testing | Department of Medical and Surgical Sciences, University of Bologna | Sep 01, 2023 | PM2(Supporting)+BP1(Strong) according to ACMG/AMP classification guidelines specified for BRCA1 & BRCA2 (Classification Criteria V1.0.0 2023-09-08 - https://cspec.genome.network/cspec/ui/svi/affiliation/50087) (PMID: 38160042) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at