rs3218438

Positions:

• chr7-152666141-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.40-5359A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0687 in 152,294 control chromosomes in the GnomAD database, including 437 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 0.069 (437 hom., cov: 33)
• Consequence: XRCC2 NM_005431.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.488

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC2	NM_005431.2	c.40-5359A>G		intron_variant		ENST00000359321.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC2	ENST00000359321.2	c.40-5359A>G		intron_variant		1	NM_005431.2	P1
XRCC2	ENST00000698506.1	c.-48+9900A>G		intron_variant
XRCC2	ENST00000698507.1	n.108-5359A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0687 AC: 10458 AN: 152176 Hom.: 437 Cov.: 33

Gnomad AFR AF: 0.0358

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0616

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0443

Gnomad FIN AF: 0.0685

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0955

Gnomad OTH AF: 0.0669

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

GnomAD4 genome AF: 0.0687 AC: 10460 AN: 152294 Hom.: 437 Cov.: 33 AF XY: 0.0665 AC XY: 4953 AN XY: 74468

Gnomad4 AFR AF: 0.0358

Gnomad4 AMR AF: 0.0615

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0448

Gnomad4 FIN AF: 0.0685

Gnomad4 NFE AF: 0.0955

Gnomad4 OTH AF: 0.0662

Alfa AF: 0.0801 Hom.: 69

Bravo AF: 0.0660

Asia WGS AF: 0.0240 AC: 83 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.0
DANN	Benign	0.81

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: rs3218438; hg19: chr7-152363226;