rs757088844
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000059.4(BRCA2):āc.8879A>Gā(p.Gln2960Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_000059.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BRCA2 | NM_000059.4 | c.8879A>G | p.Gln2960Arg | missense_variant | 22/27 | ENST00000380152.8 | NP_000050.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BRCA2 | ENST00000380152.8 | c.8879A>G | p.Gln2960Arg | missense_variant | 22/27 | 5 | NM_000059.4 | ENSP00000369497.3 | ||
BRCA2 | ENST00000530893.7 | c.8510A>G | p.Gln2837Arg | missense_variant | 22/27 | 1 | ENSP00000499438.2 | |||
BRCA2 | ENST00000614259.2 | n.*937A>G | non_coding_transcript_exon_variant | 21/26 | 2 | ENSP00000506251.1 | ||||
BRCA2 | ENST00000614259.2 | n.*937A>G | 3_prime_UTR_variant | 21/26 | 2 | ENSP00000506251.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250274Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135296
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461254Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726912
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary breast ovarian cancer syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 01, 2017 | This variant is present in population databases (rs757088844, ExAC 0.002%) but has not been reported in the literature in individuals with a BRCA2-related disease. This sequence change replaces glutamine with arginine at codon 2960 of the BRCA2 protein (p.Gln2960Arg). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and arginine. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at