rs2106776

Positions:

• chr7-152675839-G-A

Variant summary

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

The NM_005431.2(XRCC2):​c.39+202C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 151,836 control chromosomes in the GnomAD database, including 16,976 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.46 (16976 hom., cov: 31)
• Consequence: XRCC2 NM_005431.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0770

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=-0.92).
• BP6: Variant 7-152675839-G-A is Benign according to our data. Variant chr7-152675839-G-A is described in ClinVar as [Benign]. Clinvar id is 679699.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC2	NM_005431.2	c.39+202C>T		intron_variant		ENST00000359321.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC2	ENST00000359321.2	c.39+202C>T		intron_variant		1	NM_005431.2	P1
XRCC2	ENST00000698506.1	c.-48+202C>T		intron_variant
XRCC2	ENST00000698507.1	n.107+202C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70094 AN: 151718 Hom.: 16955 Cov.: 31

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.351

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.438

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

GnomAD4 genome AF: 0.462 AC: 70149 AN: 151836 Hom.: 16976 Cov.: 31 AF XY: 0.456 AC XY: 33815 AN XY: 74214

Gnomad4 AFR AF: 0.592

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.351

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.436

Alfa AF: 0.448 Hom.: 1936

Bravo AF: 0.463

Asia WGS AF: 0.372 AC: 1291 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

Jun 15, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.8
DANN	Benign	0.85

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: rs2106776; hg19: chr7-152372924;