rs41296835

Positions:

• chr2-216205503-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_021141.4(XRCC5):​c.*301A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00472 in 393,412 control chromosomes in the GnomAD database, including 33 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 0.010 (27 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (6 hom.)
• Consequence: XRCC5 NM_021141.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.359

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=-0.64).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0103 (1571/152306) while in subpopulation AFR AF= 0.0362 (1503/41552). AF 95% confidence interval is 0.0347. There are 27 homozygotes in gnomad4. There are 746 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1571 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRCC5	NM_021141.4	c.*301A>G		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.*301A>G		3_prime_UTR_variant	21/21	1	NM_021141.4	ENSP00000375977.2
XRCC5	ENST00000392133.7	c.*301A>G		3_prime_UTR_variant	23/23	5		ENSP00000375978.3

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 1572 AN: 152188 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0363

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00669

GnomAD4 exome AF: 0.00118 AC: 284 AN: 241106 Hom.: 6 Cov.: 0 AF XY: 0.00111 AC XY: 141 AN XY: 127342

Gnomad4 AFR exome AF: 0.0309

Gnomad4 AMR exome AF: 0.00183

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000205

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000608

Gnomad4 OTH exome AF: 0.00216

GnomAD4 genome AF: 0.0103 AC: 1571 AN: 152306 Hom.: 27 Cov.: 32 AF XY: 0.0100 AC XY: 746 AN XY: 74486

Gnomad4 AFR AF: 0.0362

Gnomad4 AMR AF: 0.00327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.00501 Hom.: 3

Bravo AF: 0.0115

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Benign	0.89

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: rs41296835; hg19: chr2-217070226;