rs2412547

Variant names:

• chr15-40720497-C-A
• rs2412547
• NM_002875.5:c.530+1598C>A

Variant summary

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

The NM_133487.4(RAD51):​c.533+1598C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.493 in 151,636 control chromosomes in the GnomAD database, including 19,250 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 0.49 (19250 hom., cov: 31)
• Consequence: RAD51 NM_133487.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 11 publications found

Genes affected

RAD51 (HGNC:9817): (RAD51 recombinase) 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, and are known to be involved in the homologous recombination and repair of DNA. This protein can interact with the ssDNA-binding protein RPA and RAD52, and it is thought to play roles in homologous pairing and strand transfer of DNA. This protein is also found to interact with BRCA1 and BRCA2, which may be important for the cellular response to DNA damage. BRCA2 is shown to regulate both the intracellular localization and DNA-binding ability of this protein. Loss of these controls following BRCA2 inactivation may be a key event leading to genomic instability and tumorigenesis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]

RAD51 Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group R

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• mirror movements 2

  Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• familial congenital mirror movements

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Fanconi anemia

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

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133487.4. 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
	RAD51	NM_002875.5	MANE Select	c.530+1598C>A		intron	N/A	NP_002866.2
	RAD51	NM_001164269.2		c.533+1598C>A		intron	N/A	NP_001157741.1
	RAD51	NM_133487.4		c.533+1598C>A		intron	N/A	NP_597994.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51	ENST00000267868.8	TSL:1 MANE Select	c.530+1598C>A		intron	N/A	ENSP00000267868.3
	RAD51	ENST00000532743.6	TSL:2	c.530+1598C>A		intron	N/A	ENSP00000433924.2
	RAD51	ENST00000423169.6	TSL:1	c.530+1598C>A		intron	N/A	ENSP00000406602.2

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74706 AN: 151516 Hom.: 19233 Cov.: 31

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.563

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.493 AC: 74748 AN: 151636 Hom.: 19250 Cov.: 31 AF XY: 0.504 AC XY: 37317 AN XY: 74090

African (AFR) AF: 0.364 AC: 15026 AN: 41270

American (AMR) AF: 0.601 AC: 9138 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.563 AC: 1954 AN: 3468

East Asian (EAS) AF: 0.773 AC: 3990 AN: 5160

South Asian (SAS) AF: 0.650 AC: 3124 AN: 4806

European-Finnish (FIN) AF: 0.587 AC: 6146 AN: 10464

Middle Eastern (MID) AF: 0.524 AC: 153 AN: 292

European-Non Finnish (NFE) AF: 0.497 AC: 33766 AN: 67946

Other (OTH) AF: 0.494 AC: 1040 AN: 2106

Alfa AF: 0.510 Hom.: 10569

Bravo AF: 0.491

Asia WGS AF: 0.708 AC: 2463 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.60
DANN	Benign	0.28
PhyloP100		-2.0
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: rs2412547; hg19: chr15-41012695;