rs207906

chr2-216148178-A-Gchr2-216148178-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_021141.4(XRCC5):c.1572A>G(p.Thr524=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 1,613,894 control chromosomes in the GnomAD database, including 619,911 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 0.88 (58474 hom., cov: 31)
  • Exomes 𝑓: 0.88 (561437 hom.)
• Consequence: XRCC5 NM_021141.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-0.335 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC5	NM_021141.4	c.1572A>G	p.Thr524=	synonymous_variant	14/21	ENST00000392132.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC5	ENST00000392132.7	c.1572A>G	p.Thr524=	synonymous_variant	14/21	1	NM_021141.4	P1
XRCC5	ENST00000460284.5	n.2114A>G		non_coding_transcript_exon_variant	11/18	1
XRCC5	ENST00000392133.7	c.1572A>G	p.Thr524=	synonymous_variant	16/23	5		P1

Frequencies

GnomAD3 genomes AF: 0.876 AC: 133245 AN: 152116 Hom.: 58430 Cov.: 31

Gnomad AFR AF: 0.874

Gnomad AMI AF: 0.699

Gnomad AMR AF: 0.892

Gnomad ASJ AF: 0.872

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.929

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.889

GnomAD3 exomes AF: 0.876 AC: 220009 AN: 251124 Hom.: 96566 AF XY: 0.872 AC XY: 118394 AN XY: 135720

Gnomad AFR exome AF: 0.879

Gnomad AMR exome AF: 0.892

Gnomad ASJ exome AF: 0.880

Gnomad EAS exome AF: 0.922

Gnomad SAS exome AF: 0.819

Gnomad FIN exome AF: 0.922

Gnomad NFE exome AF: 0.870

Gnomad OTH exome AF: 0.875

GnomAD4 exome AF: 0.876 AC: 1280592 AN: 1461660 Hom.: 561437 Cov.: 58 AF XY: 0.874 AC XY: 635238 AN XY: 727140

Gnomad4 AFR exome AF: 0.876

Gnomad4 AMR exome AF: 0.893

Gnomad4 ASJ exome AF: 0.878

Gnomad4 EAS exome AF: 0.918

Gnomad4 SAS exome AF: 0.817

Gnomad4 FIN exome AF: 0.919

Gnomad4 NFE exome AF: 0.876

Gnomad4 OTH exome AF: 0.878

GnomAD4 genome AF: 0.876 AC: 133347 AN: 152234 Hom.: 58474 Cov.: 31 AF XY: 0.877 AC XY: 65286 AN XY: 74436

Gnomad4 AFR AF: 0.874

Gnomad4 AMR AF: 0.891

Gnomad4 ASJ AF: 0.872

Gnomad4 EAS AF: 0.916

Gnomad4 SAS AF: 0.816

Gnomad4 FIN AF: 0.929

Gnomad4 NFE AF: 0.869

Gnomad4 OTH AF: 0.890

Alfa AF: 0.869 Hom.: 93577

Bravo AF: 0.877

Asia WGS AF: 0.859 AC: 2991 AN: 3478

EpiCase AF: 0.860

EpiControl AF: 0.864

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.43
Dann	Benign	0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs207906; hg19: chr2-217012901;