rs3218410

chr7-152669999-T-C

Variant summary

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

The NM_005431.2(XRCC2):c.39+6042A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 151,806 control chromosomes in the GnomAD database, including 2,685 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 0.18 (2685 hom., cov: 31)
• Consequence: XRCC2 NM_005431.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

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 (SAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC2	NM_005431.2	c.39+6042A>G		intron_variant		ENST00000359321.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC2	ENST00000359321.2	c.39+6042A>G		intron_variant		1	NM_005431.2	P1
XRCC2	ENST00000698506.1	c.-48+6042A>G		intron_variant
XRCC2	ENST00000698507.1	n.107+6042A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27542 AN: 151694 Hom.: 2681 Cov.: 31

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0495

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.182 AC: 27558 AN: 151806 Hom.: 2685 Cov.: 31 AF XY: 0.181 AC XY: 13404 AN XY: 74168

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.148

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.165

Alfa AF: 0.197 Hom.: 579

Bravo AF: 0.173

Asia WGS AF: 0.175 AC: 609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	4.4
Dann	Benign	0.43

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: rs3218410; hg19: chr7-152367084;