rs3218534

Positions:

• chr7-152649910-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.122-547C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 152,002 control chromosomes in the GnomAD database, including 12,612 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 0.38 (12612 hom., cov: 32)
• Consequence: XRCC2 NM_005431.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.304

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRCC2	NM_005431.2	c.122-547C>T		intron_variant		ENST00000359321.2	NP_005422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XRCC2	ENST00000359321.2	c.122-547C>T		intron_variant		1	NM_005431.2	ENSP00000352271.1
XRCC2	ENST00000495707.1	n.144-547C>T		intron_variant		1
XRCC2	ENST00000698506.1	c.-47-547C>T		intron_variant				ENSP00000513758.1

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57716 AN: 151882 Hom.: 12613 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.380 AC: 57727 AN: 152002 Hom.: 12612 Cov.: 32 AF XY: 0.386 AC XY: 28684 AN XY: 74280

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.410

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.358

Gnomad4 FIN AF: 0.613

Gnomad4 NFE AF: 0.465

Gnomad4 OTH AF: 0.389

Alfa AF: 0.409 Hom.: 2031

Bravo AF: 0.355

Asia WGS AF: 0.370 AC: 1292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3218534; hg19: chr7-152346995;