rs180869630

Variant names:

• chr17-35116913-T-C
• rs180869630
• NM_002878.4:c.263+1588A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-35116913-T-C
• chr17-35116913-T-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001142571.2(RAD51D):​c.269A>G​(p.Asp90Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,607,540 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (7 hom.)
• Consequence: RAD51D NM_001142571.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: -0.771
• Publications: 10 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007933468).
• BP6: Variant 17-35116913-T-C is Benign according to our data. Variant chr17-35116913-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 138879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00114 (174/152306) while in subpopulation NFE AF = 0.00198 (135/68020). AF 95% confidence interval is 0.00171. There are 0 homozygotes in GnomAd4. There are 78 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 174 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142571.2. 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.263+1588A>G		intron	N/A	NP_002869.3
	RAD51D	NM_001142571.2		c.269A>G	p.Asp90Gly	missense	Exon 3 of 10	NP_001136043.1	O75771-8
	RAD51D	NM_133629.3		c.144+2198A>G		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.263+1588A>G		intron	N/A	ENSP00000338790.6	O75771-1
	RAD51D	ENST00000586186.3	TSL:1	c.263+1588A>G		intron	N/A	ENSP00000468273.3	O75771-4
	ENSG00000267618	ENST00000593039.5	TSL:2	c.3+4378A>G		intron	N/A	ENSP00000466834.1	K7EN88

Frequencies

GnomAD3 genomes AF: 0.00114 AC: 174 AN: 152188 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00198

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000994 AC: 235 AN: 236304 AF XY: 0.000905

Gnomad AFR exome AF: 0.000348

Gnomad AMR exome AF: 0.000362

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000708

Gnomad NFE exome AF: 0.00187

Gnomad OTH exome AF: 0.000863

GnomAD4 exome AF: 0.00186 AC: 2713 AN: 1455234 Hom.: 7 Cov.: 31 AF XY: 0.00176 AC XY: 1270 AN XY: 723196

African (AFR) AF: 0.000271 AC: 9 AN: 33268

American (AMR) AF: 0.000688 AC: 30 AN: 43592

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25930

East Asian (EAS) AF: 0.00 AC: 0 AN: 39460

South Asian (SAS) AF: 0.0000705 AC: 6 AN: 85072

European-Finnish (FIN) AF: 0.000959 AC: 51 AN: 53170

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.00230 AC: 2552 AN: 1108780

Other (OTH) AF: 0.00106 AC: 64 AN: 60204

GnomAD4 genome AF: 0.00114 AC: 174 AN: 152306 Hom.: 0 Cov.: 32 AF XY: 0.00105 AC XY: 78 AN XY: 74476

African (AFR) AF: 0.000457 AC: 19 AN: 41560

American (AMR) AF: 0.000588 AC: 9 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000753 AC: 8 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00198 AC: 135 AN: 68020

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.00178 Hom.: 4

Bravo AF: 0.00113

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.000319 AC: 1

ESP6500EA AF: 0.00251 AC: 18

ExAC AF: 0.00105 AC: 127

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	Breast-ovarian cancer, familial, susceptibility to, 4 (5)
-	-	3	Hereditary cancer-predisposing syndrome (3)
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	RAD51D-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.0
DANN	Benign	0.92
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.0079	T
MetaSVM	Benign	-0.96	T
PhyloP100		-0.77
Sift4G	Benign	0.16	T
Vest4		0.20
MVP		0.31
MPC		0.21
ClinPred		0.0038	T
GERP RS		-3.4
gMVP		0.35
Mutation Taster		=92/8	polymorphism

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: rs180869630; hg19: chr17-33443932; COSMIC: COSV104549250;