chr13-32316406-GTCT-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6
The NM_000059.4(BRCA2):c.-39-12_-39-10delTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,492,708 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000059.4 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BRCA2 | ENST00000380152.8 | c.-39-15_-39-13delTCT | intron_variant | Intron 1 of 26 | 5 | NM_000059.4 | ENSP00000369497.3 | |||
BRCA2 | ENST00000530893.7 | c.-404-15_-404-13delTCT | intron_variant | Intron 1 of 26 | 1 | ENSP00000499438.2 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152048Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.0000455 AC: 61AN: 1340660Hom.: 0 AF XY: 0.0000446 AC XY: 30AN XY: 673308
GnomAD4 genome AF: 0.00000658 AC: 1AN: 152048Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74270
ClinVar
Submissions by phenotype
Breast-ovarian cancer, familial, susceptibility to, 2 Uncertain:2Benign:1
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The BRCA2 c.-39-12_-39-10delTCT variant is classified as VUS (BS3) -
not specified Benign:2
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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Breast and/or ovarian cancer Uncertain:1
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Malignant tumor of breast Uncertain:1
The BRCA2, EXON02, c.-39-12_-39-10delTCT variant was not identified in the literature, but was identified in dbSNP (ID: rs276174798) “With non-pathogenic allele”, in UMD 2X as an “unclassified variant” (UV), and in the BIC database 7X as a variant with unknown clinical importance. This variant is located in the 3' splice region of the 5' UTR, which may be involved in splicing activity of Exon 2 (the first coding exon). The variant does not affect the invariant -1 and -2 positions; however, positions -3 and -5 to -12 are part of the splicing consensus sequence and variants involving these positions sometimes affect splicing. Computational prediction software (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) provide inconsistent predictions regarding splicing; however, this information is not predictive enough to rule out pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined at this time. Therefore, this variant is classified as a variant of unknown significance. -
BRCA2-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Hereditary cancer-predisposing syndrome Benign:1
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Hereditary breast ovarian cancer syndrome Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at