rs1555286271
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM1PM2PM5PP3
The NM_000059.4(BRCA2):c.7526G>A(p.Ser2509Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S2509G) 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_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRCA2 | NM_000059.4 | c.7526G>A | p.Ser2509Asn | missense_variant | 15/27 | ENST00000380152.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRCA2 | ENST00000380152.8 | c.7526G>A | p.Ser2509Asn | missense_variant | 15/27 | 5 | NM_000059.4 | A2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Malignant tumor of breast Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The BRCA2 p.Ser2509Asn variant was not identified in the literature nor was it identified in the dbSNP, Clinvitae database, Fanconi Anemia Mutation Database (LOVD), LOVD-IARC database, ARUP Laboratories BRCA Mutations Database, COSMIC, the ClinVar database, GeneInsight COGR database, the BIC database, UMD and Fanconi Anemia Mutation Database (LOVD) databases. The p.Ser2509 residue is conserved across mammals and other organisms, and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the p.Ser2509Asn variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and 2 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing. However, this information is not predictive enough to assume pathogenicity. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at