rs1483527885
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_032043.3(BRIP1):c.2464_2465insT(p.Tyr822LeufsTer10) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,186 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. Y822Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_032043.3 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRIP1 | NM_032043.3 | c.2464_2465insT | p.Tyr822LeufsTer10 | frameshift_variant | 17/20 | ENST00000259008.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRIP1 | ENST00000259008.7 | c.2464_2465insT | p.Tyr822LeufsTer10 | frameshift_variant | 17/20 | 1 | NM_032043.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152186Hom.: 0 Cov.: 31
GnomAD4 exome Cov.: 30
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152186Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74344
ClinVar
Submissions by phenotype
Familial cancer of breast Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Jun 06, 2023 | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Aug 30, 2022 | - - |
Familial cancer of breast;C1836860:Fanconi anemia complementation group J Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2022 | This sequence change creates a premature translational stop signal (p.Tyr822Leufs*10) in the BRIP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRIP1 are known to be pathogenic (PMID: 16116423, 17033622, 21964575). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 530329). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.1%). - |
Hereditary cancer-predisposing syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Breast Care Center, Daerim St. Mary`s Hospital | Jul 26, 2023 | The BRIP1:c.2464dupT variant was located in exon 17 of the BRIP1 gene, which predicts to lead to NMD (nonsense-mediated mRNA decay) and loss-of-function resulting from a frameshift. Its frequency is extremely low in gnomAD genomes/exomes. The previous classification in ClinVar is as a pathogenic variant. The patient is a 58-year-old Korean male diagnosed with papillary DCIS breast cancer. He has a family history of colon cancer in his mother, larynx, and pancreatic cancer in second-degree relatives on his paternal side. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at