rs9901455

Variant names:

• chr17-35118530-G-A
• rs9901455
• NM_002878.4:c.234C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-35118530-G-A
• chr17-35118530-G-C

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_002878.4(RAD51D):​c.234C>T​(p.Ser78Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0971 in 1,613,868 control chromosomes in the GnomAD database, including 10,503 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2581 hom., cov: 32)
  • Exomes 𝑓: 0.091 (7922 hom.)
• Consequence: RAD51D NM_002878.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: 1.68
• Publications: 25 publications found

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]

RAD51D Gene-Disease associations (from GenCC):

• RAD51D-related cancer predisposition

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• breast-ovarian cancer, familial, susceptibility to, 4

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• hereditary breast ovarian cancer syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000267618 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.19).
• BP6: Variant 17-35118530-G-A is Benign according to our data. Variant chr17-35118530-G-A is described in ClinVar as Benign. ClinVar VariationId is 183785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.67 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002878.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51D	NM_002878.4	MANE Select	c.234C>T	p.Ser78Ser	synonymous	Exon 3 of 10	NP_002869.3
	RAD51D	NM_001142571.2		c.144+581C>T		intron	N/A	NP_001136043.1	O75771-8
	RAD51D	NM_133629.3		c.144+581C>T		intron	N/A	NP_598332.1	O75771-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51D	ENST00000345365.11	TSL:1 MANE Select	c.234C>T	p.Ser78Ser	synonymous	Exon 3 of 10	ENSP00000338790.6	O75771-1
	RAD51D	ENST00000586186.3	TSL:1	c.234C>T	p.Ser78Ser	synonymous	Exon 3 of 9	ENSP00000468273.3	O75771-4
	ENSG00000267618	ENST00000593039.5	TSL:2	c.3+2761C>T		intron	N/A	ENSP00000466834.1	K7EN88

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23683 AN: 152030 Hom.: 2577 Cov.: 32

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.0864

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0827

Gnomad OTH AF: 0.137

GnomAD2 exomes AF: 0.116 AC: 29273 AN: 251448 AF XY: 0.111

Gnomad AFR exome AF: 0.306

Gnomad AMR exome AF: 0.104

Gnomad ASJ exome AF: 0.140

Gnomad EAS exome AF: 0.230

Gnomad FIN exome AF: 0.112

Gnomad NFE exome AF: 0.0821

Gnomad OTH exome AF: 0.111

GnomAD4 exome AF: 0.0910 AC: 133000 AN: 1461720 Hom.: 7922 Cov.: 33 AF XY: 0.0901 AC XY: 65551 AN XY: 727166

African (AFR) AF: 0.304 AC: 10164 AN: 33476

American (AMR) AF: 0.107 AC: 4790 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 3714 AN: 26136

East Asian (EAS) AF: 0.261 AC: 10374 AN: 39700

South Asian (SAS) AF: 0.0866 AC: 7466 AN: 86250

European-Finnish (FIN) AF: 0.109 AC: 5834 AN: 53396

Middle Eastern (MID) AF: 0.130 AC: 751 AN: 5768

European-Non Finnish (NFE) AF: 0.0752 AC: 83623 AN: 1111882

Other (OTH) AF: 0.104 AC: 6284 AN: 60390

GnomAD4 genome AF: 0.156 AC: 23705 AN: 152148 Hom.: 2581 Cov.: 32 AF XY: 0.157 AC XY: 11649 AN XY: 74406

African (AFR) AF: 0.300 AC: 12430 AN: 41496

American (AMR) AF: 0.125 AC: 1917 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 550 AN: 3468

East Asian (EAS) AF: 0.227 AC: 1171 AN: 5158

South Asian (SAS) AF: 0.0860 AC: 414 AN: 4812

European-Finnish (FIN) AF: 0.119 AC: 1259 AN: 10604

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0827 AC: 5625 AN: 68010

Other (OTH) AF: 0.141 AC: 297 AN: 2110

Alfa AF: 0.112 Hom.: 714

Bravo AF: 0.162

Asia WGS AF: 0.147 AC: 513 AN: 3478

EpiCase AF: 0.0837

EpiControl AF: 0.0830

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	Breast-ovarian cancer, familial, susceptibility to, 4 (3)
-	-	3	Hereditary cancer-predisposing syndrome (3)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.19
CADD	Benign	12
DANN	Benign	0.84
PhyloP100		1.7
Mutation Taster		=295/5	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9901455; hg19: chr17-33445549; COSMIC: COSV99338663; COSMIC: COSV99338663;