chr2-216205653-A-G

Variant names:

• chr2-216205653-A-G
• rs1051685
• NM_021141.4:c.*451A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021141.4(XRCC5):​c.*451A>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 0.173 in 157,042 control chromosomes in the GnomAD database, including 2,979 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 0.17 (2949 hom., cov: 32)
  • Exomes 𝑓: 0.11 (30 hom.)
• Consequence: XRCC5 NM_021141.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.41
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021141.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC5	NM_021141.4	MANE Select	c.*451A>G		3_prime_UTR	Exon 21 of 21	NP_066964.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC5	ENST00000392132.7	TSL:1 MANE Select	c.*451A>G		3_prime_UTR	Exon 21 of 21	ENSP00000375977.2
	XRCC5	ENST00000392133.7	TSL:5	c.*451A>G		3_prime_UTR	Exon 23 of 23	ENSP00000375978.3
	XRCC5	ENST00000460284.5	TSL:1	n.*230A>G		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26550 AN: 151992 Hom.: 2935 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0717

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.142

GnomAD4 exome AF: 0.112 AC: 554 AN: 4932 Hom.: 30 Cov.: 0 AF XY: 0.122 AC XY: 319 AN XY: 2616

African (AFR) AF: 0.351 AC: 26 AN: 74

American (AMR) AF: 0.100 AC: 50 AN: 498

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 13 AN: 112

East Asian (EAS) AF: 0.0671 AC: 11 AN: 164

South Asian (SAS) AF: 0.156 AC: 66 AN: 422

European-Finnish (FIN) AF: 0.128 AC: 20 AN: 156

Middle Eastern (MID) AF: 0.111 AC: 2 AN: 18

European-Non Finnish (NFE) AF: 0.104 AC: 342 AN: 3292

Other (OTH) AF: 0.122 AC: 24 AN: 196

GnomAD4 genome AF: 0.175 AC: 26617 AN: 152110 Hom.: 2949 Cov.: 32 AF XY: 0.175 AC XY: 12999 AN XY: 74362

African (AFR) AF: 0.319 AC: 13225 AN: 41442

American (AMR) AF: 0.120 AC: 1832 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 476 AN: 3470

East Asian (EAS) AF: 0.0721 AC: 374 AN: 5190

South Asian (SAS) AF: 0.174 AC: 837 AN: 4824

European-Finnish (FIN) AF: 0.113 AC: 1202 AN: 10594

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8285 AN: 68000

Other (OTH) AF: 0.141 AC: 297 AN: 2108

Alfa AF: 0.136 Hom.: 6570

Bravo AF: 0.180

Asia WGS AF: 0.143 AC: 498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0070
DANN	Benign	0.30
PhyloP100		-4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1051685; hg19: chr2-217070376;