rs3218385

chr7-152676148-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000698506.1(XRCC2):c.-155T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0498 in 1,607,010 control chromosomes in the GnomAD database, including 2,345 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.062 (365 hom., cov: 33)
  • Exomes 𝑓: 0.048 (1980 hom.)
• Consequence: XRCC2 ENST00000698506.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.33

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 7-152676148-A-C is Benign according to our data. Variant chr7-152676148-A-C is described in ClinVar as [Benign]. Clinvar id is 1261765.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC2	NM_005431.2			upstream_gene_variant		ENST00000359321.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC2	ENST00000698506.1	c.-155T>G		5_prime_UTR_variant	1/2
XRCC2	ENST00000359321.2			upstream_gene_variant		1	NM_005431.2	P1
XRCC2	ENST00000698507.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0621 AC: 9422 AN: 151844 Hom.: 359 Cov.: 33

Gnomad AFR AF: 0.0980

Gnomad AMI AF: 0.0870

Gnomad AMR AF: 0.0484

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.0550

Gnomad FIN AF: 0.0163

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0458

Gnomad OTH AF: 0.0628

GnomAD4 exome AF: 0.0485 AC: 70568 AN: 1455050 Hom.: 1980 Cov.: 29 AF XY: 0.0488 AC XY: 35324 AN XY: 724238

Gnomad4 AFR exome AF: 0.0971

Gnomad4 AMR exome AF: 0.0451

Gnomad4 ASJ exome AF: 0.0592

Gnomad4 EAS exome AF: 0.0885

Gnomad4 SAS exome AF: 0.0528

Gnomad4 FIN exome AF: 0.0178

Gnomad4 NFE exome AF: 0.0462

Gnomad4 OTH exome AF: 0.0552

GnomAD4 genome AF: 0.0621 AC: 9438 AN: 151960 Hom.: 365 Cov.: 33 AF XY: 0.0610 AC XY: 4531 AN XY: 74274

Gnomad4 AFR AF: 0.0981

Gnomad4 AMR AF: 0.0481

Gnomad4 ASJ AF: 0.0599

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.0548

Gnomad4 FIN AF: 0.0163

Gnomad4 NFE AF: 0.0459

Gnomad4 OTH AF: 0.0650

Alfa AF: 0.0543 Hom.: 148

Bravo AF: 0.0673

Asia WGS AF: 0.0890 AC: 310 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	2.3
Dann	Benign	0.44

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: rs3218385; hg19: chr7-152373233; COSMIC: COSV63770221;