rs3218455

Positions:

• chr7-152663331-A-G

Variant summary

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

The NM_005431.2(XRCC2):​c.40-2549T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.06 in 124,536 control chromosomes in the GnomAD database, including 302 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 0.060 (302 hom., cov: 24)
• Consequence: XRCC2 NM_005431.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

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]

XRCC2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRCC2	NM_005431.2	c.40-2549T>C		intron_variant		ENST00000359321.2	NP_005422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XRCC2	ENST00000359321.2	c.40-2549T>C		intron_variant		1	NM_005431.2	ENSP00000352271.1
XRCC2	ENST00000495707.1	n.61+613T>C		intron_variant		1
XRCC2	ENST00000698506.1	c.-48+12710T>C		intron_variant				ENSP00000513758.1
XRCC2	ENST00000698507.1	n.108-2549T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0600 AC: 7466 AN: 124428 Hom.: 302 Cov.: 24

Gnomad AFR AF: 0.0178

Gnomad AMI AF: 0.0435

Gnomad AMR AF: 0.0630

Gnomad ASJ AF: 0.0927

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0358

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0842

Gnomad OTH AF: 0.0668

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

GnomAD4 genome AF: 0.0600 AC: 7468 AN: 124536 Hom.: 302 Cov.: 24 AF XY: 0.0606 AC XY: 3532 AN XY: 58240

Gnomad4 AFR AF: 0.0179

Gnomad4 AMR AF: 0.0629

Gnomad4 ASJ AF: 0.0927

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.0358

Gnomad4 NFE AF: 0.0841

Gnomad4 OTH AF: 0.0662

Alfa AF: 0.0622 Hom.: 58

Bravo AF: 0.0538

Asia WGS AF: 0.0500 AC: 173 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.4
DANN	Benign	0.74

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: rs3218455; hg19: chr7-152360416;