17-35101231-G-A
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_002878.4(RAD51D):c.873C>T(p.Arg291Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000637 in 1,614,178 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_002878.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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RAD51D | ENST00000345365.11 | c.873C>T | p.Arg291Arg | synonymous_variant | Exon 9 of 10 | 1 | NM_002878.4 | ENSP00000338790.6 | ||
ENSG00000267618 | ENST00000593039.5 | c.396C>T | p.Arg132Arg | synonymous_variant | Exon 5 of 7 | 2 | ENSP00000466834.1 |
Frequencies
GnomAD3 genomes AF: 0.00365 AC: 556AN: 152180Hom.: 4 Cov.: 32
GnomAD3 exomes AF: 0.000879 AC: 221AN: 251424Hom.: 0 AF XY: 0.000655 AC XY: 89AN XY: 135892
GnomAD4 exome AF: 0.000324 AC: 473AN: 1461880Hom.: 4 Cov.: 31 AF XY: 0.000272 AC XY: 198AN XY: 727236
GnomAD4 genome AF: 0.00365 AC: 556AN: 152298Hom.: 4 Cov.: 32 AF XY: 0.00340 AC XY: 253AN XY: 74472
ClinVar
Submissions by phenotype
Breast-ovarian cancer, familial, susceptibility to, 4 Benign:4
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This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -
not specified Benign:3
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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. -
Hereditary cancer-predisposing syndrome Benign:2
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This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Breast and/or ovarian cancer Benign:1
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not provided Benign:1
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Malignant tumor of breast Benign:1
The RAD51D p.Arg291= variant was not identified in the literature nor was it identified in the Cosmic and Zhejiang Colon Cancer Database. The variant was also identified in dbSNP (ID: rs140848654) “With Likely benign allele”, ClinVar (classified benign by GeneDx, Invitae, Counsyl; and likely benign by Ambry Genetics, Illumina), Clinvitae (4X) and in control databases in 325 (2 homozygous) of 277174 chromosomes at a frequency of 0.001 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017), being identified in the following populations: African in 301 (2 homozygous) of 24032 chromosomes (frequency: 0.01), Other in 3 of 6460 chromosomes (frequency: 0005), Latino in 17 of 34418 chromosomes (frequency: 0.0005), European Non-Finnish in 4 of 126672 chromosomes (frequency: 00003). The p.Arg291= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at