rs200487648
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_002878.4(RAD51D):c.27C>T(p.Cys9Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,612,382 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
RAD51D
NM_002878.4 synonymous
NM_002878.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.10
Genes affected
RAD51D (HGNC:9823): (RAD51 paralog D) The protein encoded by this gene is a member of the RAD51 protein family. RAD51 family members are highly similar to bacterial RecA and Saccharomyces cerevisiae Rad51, which are known to be involved in the homologous recombination and repair of DNA. This protein forms a complex with several other members of the RAD51 family, including RAD51L1, RAD51L2, and XRCC2. The protein complex formed with this protein has been shown to catalyze homologous pairing between single- and double-stranded DNA, and is thought to play a role in the early stage of recombinational repair of DNA. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream ring finger and FYVE-like domain containing 1 (RFFL) gene. [provided by RefSeq, Jan 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
Variant 17-35119587-G-A is Benign according to our data. Variant chr17-35119587-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 185973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.11 with no splicing effect.
BS2
High AC in GnomAdExome4 at 18 AD gene.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152210Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000485 AC: 12AN: 247528Hom.: 0 AF XY: 0.0000447 AC XY: 6AN XY: 134210
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GnomAD4 exome AF: 0.0000123 AC: 18AN: 1460054Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 726432
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152328Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74498
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ClinVar
Significance: Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary cancer-predisposing syndrome Benign:3
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | Nov 22, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 12, 2014 | 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. - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Nov 16, 2015 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 04, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Mar 03, 2020 | - - |
Malignant tumor of breast Benign:1
Likely benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The RAD51D p.Cys9= variant was not identified in the literature. The variant was identified in dbSNP (ID: rs200487648) as “With Likely benign allele” and ClinVar (classified likely benign by Ambry Genetics, Invitae, Color and GeneDx). The variant was identified in control databases in 10 of 242490 chromosomes at a frequency of 0.00004 (Genome Aggregation Database Feb 27, 2017), observed in the following populations: Other in 1 of 5456 chromosomes (freq: 0.0002) and East Asian in 9 of 17198 chromosomes (freq: 0.0005), while not observed in the African, Latino, European, Ashkenazi Jewish, Finnish, or South Asian populations. The p.Cys9= 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 addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. 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. - |
Breast-ovarian cancer, familial, susceptibility to, 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 24, 2024 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at