13-32398153-T-G
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_000059.4(BRCA2):c.9649-9T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000374 in 1,603,374 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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 -5 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BRCA2 | ENST00000380152.8 | c.9649-9T>G | intron_variant | Intron 26 of 26 | 5 | NM_000059.4 | ENSP00000369497.3 | |||
BRCA2 | ENST00000530893.7 | c.9280-9T>G | intron_variant | Intron 26 of 26 | 1 | ENSP00000499438.2 | ||||
BRCA2 | ENST00000614259.2 | n.*1707-9T>G | intron_variant | Intron 25 of 25 | 2 | ENSP00000506251.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152262Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000207 AC: 3AN: 1451112Hom.: 0 Cov.: 30 AF XY: 0.00000415 AC XY: 3AN XY: 722138
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152262Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74396
ClinVar
Submissions by phenotype
Inherited breast cancer and ovarian cancer Uncertain:1
BP4 -
not provided Uncertain:1
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not specified Benign:1
Variant summary: BRCA2 c.9649-9T>G alters a conserved nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. To our knowledge, no occurrence of c.9649-9T>G in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 491385). Based on the evidence outlined above, the variant was classified as likely benign. -
Breast-ovarian cancer, familial, susceptibility to, 2 Benign:1
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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