14-68563935-C-G

Variant names:

• chr14-68563935-C-G
• rs17105852
• ENST00000487861.5:c.1037-47071C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000487861.5(RAD51B):​c.1037-47071C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 829,958 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• primary ovarian failure

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

LOC124903335 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124903335	XR_007064224.1	n.1316G>C		non_coding_transcript_exon_variant	Exon 1 of 2
LOC124903335	XR_007064226.1	n.1316G>C		non_coding_transcript_exon_variant	Exon 1 of 3
RAD51B	NM_001321821.2	c.1037-47071C>G		intron_variant	Intron 10 of 10		NP_001308750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000487861.5	c.1037-47071C>G		intron_variant	Intron 10 of 10	1		ENSP00000419881.1
RAD51B	ENST00000487270.5	c.1037-30550C>G		intron_variant	Intron 10 of 10	1		ENSP00000419471.1
RAD51B	ENST00000488612.5	c.1037-86846C>G		intron_variant	Intron 10 of 11	1		ENSP00000420061.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000157 AC: 13 AN: 829958 Hom.: 0 Cov.: 28 AF XY: 0.0000130 AC XY: 5 AN XY: 383410

African (AFR) AF: 0.00 AC: 0 AN: 15706

American (AMR) AF: 0.00 AC: 0 AN: 982

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5134

East Asian (EAS) AF: 0.00 AC: 0 AN: 3614

South Asian (SAS) AF: 0.00 AC: 0 AN: 16384

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 276

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1620

European-Non Finnish (NFE) AF: 0.0000171 AC: 13 AN: 759050

Other (OTH) AF: 0.00 AC: 0 AN: 27192

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	16
DANN	Benign	0.81
PhyloP100		0.18

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17105852; hg19: chr14-69030652;