rs207906

Variant names:

• chr2-216148178-A-G
• rs207906
• NM_021141.4:c.1572A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-216148178-A-G
• chr2-216148178-A-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_021141.4(XRCC5):​c.1572A>G​(p.Thr524Thr) 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
• Publications: 40 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
XRCC5	NM_021141.4	c.1572A>G	p.Thr524Thr	synonymous_variant	Exon 14 of 21	ENST00000392132.7	NP_066964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC5	ENST00000392132.7	c.1572A>G	p.Thr524Thr	synonymous_variant	Exon 14 of 21	1	NM_021141.4	ENSP00000375977.2
XRCC5	ENST00000460284.5	n.2114A>G		non_coding_transcript_exon_variant	Exon 11 of 18	1
XRCC5	ENST00000392133.7	c.1572A>G	p.Thr524Thr	synonymous_variant	Exon 16 of 23	5		ENSP00000375978.3

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

GnomAD2 exomes AF: 0.876 AC: 220009 AN: 251124 AF XY: 0.872

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 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

African (AFR) AF: 0.876 AC: 29308 AN: 33456

American (AMR) AF: 0.893 AC: 39878 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.878 AC: 22950 AN: 26130

East Asian (EAS) AF: 0.918 AC: 36434 AN: 39686

South Asian (SAS) AF: 0.817 AC: 70437 AN: 86218

European-Finnish (FIN) AF: 0.919 AC: 49103 AN: 53414

Middle Eastern (MID) AF: 0.860 AC: 4959 AN: 5768

European-Non Finnish (NFE) AF: 0.876 AC: 974478 AN: 1111928

Other (OTH) AF: 0.878 AC: 53045 AN: 60384

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

African (AFR) AF: 0.874 AC: 36285 AN: 41522

American (AMR) AF: 0.891 AC: 13640 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.872 AC: 3024 AN: 3468

East Asian (EAS) AF: 0.916 AC: 4749 AN: 5182

South Asian (SAS) AF: 0.816 AC: 3941 AN: 4828

European-Finnish (FIN) AF: 0.929 AC: 9847 AN: 10604

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.869 AC: 59087 AN: 68016

Other (OTH) AF: 0.890 AC: 1876 AN: 2108

Alfa AF: 0.870 Hom.: 114286

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
PhyloP100		-0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs207906; hg19: chr2-217012901; COSMIC: COSV108234397;