14-67823562-A-C

Position:

• chr14-67823562-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_133510.4(RAD51B):​c.19A>C​(p.Lys7Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: RAD51B NM_133510.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.91

Genes affected

RAD51B (HGNC:9822): (RAD51 paralog B) The protein encoded by this gene is a member of the RAD51 protein family. RAD51 family members are evolutionarily conserved proteins essential for DNA repair by homologous recombination. This protein has been shown to form a stable heterodimer with the family member RAD51C, which further interacts with the other family members, such as RAD51, XRCC2, and XRCC3. Overexpression of this gene was found to cause cell cycle G1 delay and cell apoptosis, which suggested a role of this protein in sensing DNA damage. Rearrangements between this locus and high mobility group AT-hook 2 (HMGA2, GeneID 8091) have been observed in uterine leiomyomata. [provided by RefSeq, Mar 2016]

RAD51B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1841934).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD51B	NM_133510.4	c.19A>C	p.Lys7Gln	missense_variant	2/11	ENST00000471583.6	NP_598194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000471583.6	c.19A>C	p.Lys7Gln	missense_variant	2/11	1	NM_133510.4	ENSP00000418859.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461528 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727062

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 10, 2024

The c.19A>C (p.K7Q) alteration is located in exon 2 (coding exon 1) of the RAD51B gene. This alteration results from a A to C substitution at nucleotide position 19, causing the lysine (K) at amino acid position 7 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.0014	T;.;T;T;.;.;.
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.044
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	D;D;D;D;D;D;D
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.18	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	.;N;N;.;N;.;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.0	N;N;N;N;N;N;N
REVEL	Benign	0.092
Sift	Benign	0.21	T;T;T;T;T;T;T
Sift4G	Benign	0.19	T;T;T;T;T;T;T
Polyphen		0.022	B;B;B;.;B;.;.
Vest4		0.19
MutPred		0.36		Loss of MoRF binding (P = 0.0405);Loss of MoRF binding (P = 0.0405);Loss of MoRF binding (P = 0.0405);Loss of MoRF binding (P = 0.0405);Loss of MoRF binding (P = 0.0405);Loss of MoRF binding (P = 0.0405);Loss of MoRF binding (P = 0.0405);
MVP		0.58
MPC		0.23
ClinPred		0.60	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-68290279;