rs3218493

chr7-152656578-G-C

Variant summary

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

The NM_005431.2(XRCC2):c.121+4123C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0618 in 147,996 control chromosomes in the GnomAD database, including 572 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 0.062 (572 hom., cov: 32)
• Consequence: XRCC2 NM_005431.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC2	NM_005431.2	c.121+4123C>G		intron_variant		ENST00000359321.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC2	ENST00000359321.2	c.121+4123C>G		intron_variant		1	NM_005431.2	P1
XRCC2	ENST00000495707.1	n.143+4123C>G		intron_variant, non_coding_transcript_variant		1
XRCC2	ENST00000698506.1	c.-47-7215C>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0617 AC: 9131 AN: 147874 Hom.: 568 Cov.: 32

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0223

Gnomad MID AF: 0.0645

Gnomad NFE AF: 0.0462

Gnomad OTH AF: 0.0864

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0618 AC: 9146 AN: 147996 Hom.: 572 Cov.: 32 AF XY: 0.0653 AC XY: 4695 AN XY: 71942

Gnomad4 AFR AF: 0.0198

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0223

Gnomad4 NFE AF: 0.0462

Gnomad4 OTH AF: 0.0879

Alfa AF: 0.0515 Hom.: 42

Bravo AF: 0.0731

Asia WGS AF: 0.154 AC: 534 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.1
Dann	Benign	0.63

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: rs3218493; hg19: chr7-152353663;