rs797044557

chr15-40709087-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_002875.5(RAD51):c.406A>T(p.Ile136Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as not provided (no stars). Synonymous variant affecting the same amino acid position (i.e. I136I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAD51 NM_002875.5 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 2.40

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, RAD51

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD51	NM_002875.5	c.406A>T	p.Ile136Phe	missense_variant	5/10	ENST00000267868.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD51	ENST00000267868.8	c.406A>T	p.Ile136Phe	missense_variant	5/10	1	NM_002875.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Mirror movements 2 Other:1

not provided, no classification provided

literature only

GeneReviews

-

May be associated with a higher risk of CMM. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.057	T;.;T;.;.;.
Eigen	Benign	0.010
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.96	D;D;D;.;D;.
M_CAP	Benign	0.048	D
MetaRNN	Uncertain	0.62	D;D;D;D;D;D
MetaSVM	Benign	-0.82	T
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.4	N;N;D;D;D;.
REVEL	Benign	0.26
Sift	Uncertain	0.0020	D;D;D;D;D;.
Sift4G	Uncertain	0.021	D;T;T;T;T;.
Polyphen		0.088, 0.0020	.;B;B;.;.;.
Vest4		0.60, 0.62, 0.61, 0.61
MutPred		0.77		Gain of ubiquitination at K133 (P = 0.0931);Gain of ubiquitination at K133 (P = 0.0931);Gain of ubiquitination at K133 (P = 0.0931);.;.;Gain of ubiquitination at K133 (P = 0.0931);
MVP		0.62
MPC		1.5
ClinPred		0.77	D
GERP RS		5.7
Varity_R		0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs797044557; hg19: chr15-41001285;