rs3218556

chr7-152646516-G-A

Variant summary

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

The NM_005431.2(XRCC2):c.*2126C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,140 control chromosomes in the GnomAD database, including 1,168 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 0.10 (1168 hom., cov: 33)
  • Exomes 𝑓: 0.014 (0 hom.)
• Consequence: XRCC2 NM_005431.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137

Genes affected

XRCC2 (HGNC:12829): (X-ray repair cross complementing 2) This gene encodes a member of the RecA/Rad51-related protein family that participates in homologous recombination to maintain chromosome stability and repair DNA damage. This gene is involved in the repair of DNA double-strand breaks by homologous recombination and it functionally complements Chinese hamster irs1, a repair-deficient mutant that exhibits hypersensitivity to a number of different DNA-damaging agents. [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 (AMR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC2	NM_005431.2	c.*2126C>T		3_prime_UTR_variant	3/3	ENST00000359321.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC2	ENST00000359321.2	c.*2126C>T		3_prime_UTR_variant	3/3	1	NM_005431.2	P1
XRCC2	ENST00000495707.1	n.2991C>T		non_coding_transcript_exon_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15429 AN: 151954 Hom.: 1159 Cov.: 33

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0200

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0461

Gnomad OTH AF: 0.113

GnomAD4 exome AF: 0.0143 AC: 1 AN: 70 Hom.: 0 Cov.: 0 AF XY: 0.0208 AC XY: 1 AN XY: 48

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.102 AC: 15464 AN: 152070 Hom.: 1168 Cov.: 33 AF XY: 0.103 AC XY: 7654 AN XY: 74340

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.173

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0200

Gnomad4 NFE AF: 0.0461

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0787 Hom.: 95

Bravo AF: 0.121

Asia WGS AF: 0.166 AC: 577 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	4.1
Dann	Benign	0.73

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: rs3218556; hg19: chr7-152343601; COSMIC: COSV63770431;