rs1555286076
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000059.4(BRCA2):c.7316G>A(p.Gly2439Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,598 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G2439V) has been classified as Uncertain significance.
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 | UniProt |
---|---|---|---|---|---|---|---|
BRCA2 | NM_000059.4 | c.7316G>A | p.Gly2439Glu | missense_variant | 14/27 | ENST00000380152.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRCA2 | ENST00000380152.8 | c.7316G>A | p.Gly2439Glu | missense_variant | 14/27 | 5 | NM_000059.4 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461598Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1AN XY: 727108
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary breast ovarian cancer syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 26, 2020 | 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 glutamic acid 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: 576301). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with glutamic acid at codon 2439 of the BRCA2 protein (p.Gly2439Glu). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and glutamic acid. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at