rs6941

Positions:

• chr2-216205929-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021141.4(XRCC5):​c.*727C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,134 control chromosomes in the GnomAD database, including 1,207 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 0.12 (1207 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: XRCC5 NM_021141.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.27

Genes affected

XRCC5 (HGNC:12833): (X-ray repair cross complementing 5) The protein encoded by this gene is the 80-kilodalton subunit of the Ku heterodimer protein which is also known as ATP-dependant DNA helicase II or DNA repair protein XRCC5. Ku is the DNA-binding component of the DNA-dependent protein kinase, and it functions together with the DNA ligase IV-XRCC4 complex in the repair of DNA double-strand break by non-homologous end joining and the completion of V(D)J recombination events. This gene functionally complements Chinese hamster xrs-6, a mutant defective in DNA double-strand break repair and in ability to undergo V(D)J recombination. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRCC5	NM_021141.4	c.*727C>A		3_prime_UTR_variant	21/21	ENST00000392132.7	NP_066964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XRCC5	ENST00000392132.7	c.*727C>A		3_prime_UTR_variant	21/21	1	NM_021141.4	ENSP00000375977	P1
XRCC5	ENST00000392133.7	c.*727C>A		3_prime_UTR_variant	23/23	5		ENSP00000375978	P1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17835 AN: 152014 Hom.: 1207 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.0834

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.117 AC: 17851 AN: 152132 Hom.: 1207 Cov.: 32 AF XY: 0.118 AC XY: 8778 AN XY: 74402

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.0833

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.107

Alfa AF: 0.103 Hom.: 697

Bravo AF: 0.111

Asia WGS AF: 0.205 AC: 711 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.20
DANN	Benign	0.68

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: rs6941; hg19: chr2-217070652;