rs3218454

chr7-152663335-T-Achr7-152663335-T-G

Variant summary

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

The NM_005431.2(XRCC2):c.40-2553A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0635 in 107,398 control chromosomes in the GnomAD database, including 267 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 0.064 (267 hom., cov: 21)
• Consequence: XRCC2 NM_005431.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.093 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC2	NM_005431.2	c.40-2553A>T		intron_variant		ENST00000359321.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC2	ENST00000359321.2	c.40-2553A>T		intron_variant		1	NM_005431.2	P1
XRCC2	ENST00000495707.1	n.61+609A>T		intron_variant, non_coding_transcript_variant		1
XRCC2	ENST00000698506.1	c.-48+12706A>T		intron_variant
XRCC2	ENST00000698507.1	n.108-2553A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0635 AC: 6820 AN: 107362 Hom.: 267 Cov.: 21

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.0527

Gnomad ASJ AF: 0.0488

Gnomad EAS AF: 0.00345

Gnomad SAS AF: 0.0337

Gnomad FIN AF: 0.0615

Gnomad MID AF: 0.0108

Gnomad NFE AF: 0.0952

Gnomad OTH AF: 0.0451

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

GnomAD4 genome AF: 0.0635 AC: 6820 AN: 107398 Hom.: 267 Cov.: 21 AF XY: 0.0606 AC XY: 3094 AN XY: 51024

Gnomad4 AFR AF: 0.0173

Gnomad4 AMR AF: 0.0528

Gnomad4 ASJ AF: 0.0488

Gnomad4 EAS AF: 0.00346

Gnomad4 SAS AF: 0.0338

Gnomad4 FIN AF: 0.0615

Gnomad4 NFE AF: 0.0952

Gnomad4 OTH AF: 0.0451

Alfa AF: 0.0304 Hom.: 29

Bravo AF: 0.0505

Asia WGS AF: 0.0140 AC: 50 AN: 3422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	5.9
Dann	Benign	0.84

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: rs3218454; hg19: chr7-152360420;