NM_002878.4:c.263+2305T>C

Variant names:

• chr17-35116196-A-G
• rs9915078
• NM_002878.4:c.263+2305T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002878.4(RAD51D):​c.263+2305T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,080 control chromosomes in the GnomAD database, including 2,574 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2574 hom., cov: 32)
• Consequence: RAD51D NM_002878.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.770
• Publications: 4 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):

• breast-ovarian cancer, familial, susceptibility to, 4

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary breast carcinoma

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ENSG00000267618 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51D	NM_002878.4	MANE Select	c.263+2305T>C		intron	N/A	NP_002869.3
	RAD51D	NM_001142571.2		c.323+663T>C		intron	N/A	NP_001136043.1
	RAD51D	NM_133629.3		c.144+2915T>C		intron	N/A	NP_598332.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51D	ENST00000345365.11	TSL:1 MANE Select	c.263+2305T>C		intron	N/A	ENSP00000338790.6
	RAD51D	ENST00000586186.3	TSL:1	c.263+2305T>C		intron	N/A	ENSP00000468273.3
	ENSG00000267618	ENST00000593039.5	TSL:2	c.3+5095T>C		intron	N/A	ENSP00000466834.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23616 AN: 151962 Hom.: 2570 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.0874

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0821

Gnomad OTH AF: 0.132

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.155 AC: 23647 AN: 152080 Hom.: 2574 Cov.: 32 AF XY: 0.156 AC XY: 11620 AN XY: 74360

African (AFR) AF: 0.301 AC: 12483 AN: 41440

American (AMR) AF: 0.123 AC: 1888 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 539 AN: 3472

East Asian (EAS) AF: 0.225 AC: 1159 AN: 5158

South Asian (SAS) AF: 0.0871 AC: 420 AN: 4822

European-Finnish (FIN) AF: 0.119 AC: 1257 AN: 10590

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0820 AC: 5577 AN: 67990

Other (OTH) AF: 0.136 AC: 287 AN: 2114

Alfa AF: 0.135 Hom.: 512

Bravo AF: 0.162

Asia WGS AF: 0.146 AC: 510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.63
DANN	Benign	0.63
PhyloP100		-0.77
Mutation Taster		=100/0	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: rs9915078; hg19: chr17-33443215;