NM_000059.4:c.8487+47C>T
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000059.4(BRCA2):c.8487+47C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00265 in 1,574,010 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★★).
Frequency
Consequence
NM_000059.4 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BRCA2 | ENST00000380152.8 | c.8487+47C>T | intron_variant | Intron 19 of 26 | 5 | NM_000059.4 | ENSP00000369497.3 | |||
BRCA2 | ENST00000530893.7 | c.8118+47C>T | intron_variant | Intron 19 of 26 | 1 | ENSP00000499438.2 | ||||
BRCA2 | ENST00000614259.2 | n.*545+47C>T | intron_variant | Intron 18 of 25 | 2 | ENSP00000506251.1 |
Frequencies
GnomAD3 genomes AF: 0.0137 AC: 2082AN: 152072Hom.: 38 Cov.: 32
GnomAD3 exomes AF: 0.00355 AC: 852AN: 240012Hom.: 17 AF XY: 0.00259 AC XY: 336AN XY: 129888
GnomAD4 exome AF: 0.00147 AC: 2094AN: 1421820Hom.: 44 Cov.: 26 AF XY: 0.00128 AC XY: 905AN XY: 709134
GnomAD4 genome AF: 0.0137 AC: 2083AN: 152190Hom.: 38 Cov.: 32 AF XY: 0.0130 AC XY: 966AN XY: 74404
ClinVar
Submissions by phenotype
Breast-ovarian cancer, familial, susceptibility to, 2 Uncertain:1Benign:4
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Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.05488 (African), derived from 1000 genomes (2012-04-30). -
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not specified Benign:3
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The BRCA2 c.8487+47C>T variant was identified in the literature. The variant was also identified in dbSNP (ID: rs11571744) “With Uncertain significance allele”, with a minor allele frequency of 0.0162 (1000 Genomes Project), NHLBI Exome Sequencing Project (Exome Variant Server), Exome Aggregation Consortium (ExAC) database, Clinvitae database (X1), LOVD, the ClinVar database, GeneInsight COGR database (1X), the BIC database (2X with no clinical importance), and UMD (37X as a neutral variant). In UMD the variant was identified with a co-occurring pathogenic BRCA1 and BRCA2 variants (BRCA1 (c.1813dup (p.Ile605AsnfsX11); c.5576_5579delTTAA (p.Ile1859LysfsX3); c.1310_1313delAAGA (p.Lys437IlefsX22); BRCA2 (c.IVS16+6T>C (c.4986+6T>C); c.1488delT (p.Leu498SerfsX5)), increasing the likelihood that the c.8487+47C>T variant does not have clinical significance. In BIC database variant was reported to occur in outbred control reference groups at an allele frequency >1% (MAF>0.01), and classifies the variant as not pathogenic/low clinical significance. This variant was identified in the 1000 Genomes Project in 81 of 5000 chromosomes (frequency: 0.0162), Exome Variant Server project in 1 of 8600 European American and in 197 of 4404 African American alleles, increasing the likelihood that this may be a low frequency benign variant in certain populations of origin. The variant was also found in the Exome Aggregation Consortium (ExAC) database (released Jan 13, 2015) in 436 of 9658 chromosomes (frequency: 0.045) and nine times in homozygous state from a population of African individuals, increasing the likelihood that this may be a low frequency benign variant in certain populations of origin. The variant was also identified in 39 of 91040 European (Non-Finnish)/ Latino / South Asian/European (Finnish) individuals, increasing the likelihood this could be a low frequency benign variant. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In addition, global sequence diversity analysis identified the variant has global heterozygosity 0.018 and classified the variant as polymorphism (Wagner 1999). In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign. -
not provided Benign:2
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Familial cancer of breast 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