7-152648922-C-T

Position:

chr7-152648922-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000359321.2(XRCC2):c.563G>A(p.Arg188His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 1,614,060 control chromosomes in the GnomAD database, including 5,145 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R188C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.055 ( 336 hom., cov: 32)

Exomes 𝑓: 0.077 ( 4809 hom. )

Consequence

XRCC2
ENST00000359321.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.57

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021595955).

BP6

Variant 7-152648922-C-T is Benign according to our data. Variant chr7-152648922-C-T is described in ClinVar as [Benign]. Clinvar id is 486723.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRCC2	NM_005431.2 linkuse as main transcript	c.563G>A	p.Arg188His	missense_variant	3/3	ENST00000359321.2	NP_005422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
XRCC2	ENST00000359321.2 linkuse as main transcript	c.563G>A	p.Arg188His	missense_variant	3/3	1	NM_005431.2	ENSP00000352271	P1
XRCC2	ENST00000495707.1 linkuse as main transcript	n.585G>A		non_coding_transcript_exon_variant	3/3	1
XRCC2	ENST00000698506.1 linkuse as main transcript	c.395G>A	p.Arg132His	missense_variant	2/2			ENSP00000513758

Frequencies

GnomAD3 genomes

AF:

0.0549

AC:

8352

AN:

152070

Hom.:

338

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0155

Gnomad AMI

AF:

0.0428

Gnomad AMR

AF:

0.0577

Gnomad ASJ

AF:

0.0910

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.0301

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0803

Gnomad OTH

AF:

0.0657

GnomAD3 exomes

AF:

0.0636

AC:

15999

AN:

251360

Hom.:

678

AF XY:

0.0685

AC XY:

9303

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.0119

Gnomad AMR exome

AF:

0.0410

Gnomad ASJ exome

AF:

0.0834

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.106

Gnomad FIN exome

AF:

0.0339

Gnomad NFE exome

AF:

0.0803

Gnomad OTH exome

AF:

0.0704

GnomAD4 exome

AF:

0.0768

AC:

112337

AN:

1461872

Hom.:

4809

Cov.:

AF XY:

0.0783

AC XY:

56917

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0131

Gnomad4 AMR exome

AF:

0.0425

Gnomad4 ASJ exome

AF:

0.0853

Gnomad4 EAS exome

AF:

0.000302

Gnomad4 SAS exome

AF:

0.106

Gnomad4 FIN exome

AF:

0.0355

Gnomad4 NFE exome

AF:

0.0824

Gnomad4 OTH exome

AF:

0.0755

GnomAD4 genome

AF:

0.0549

AC:

8349

AN:

152188

Hom.:

336

Cov.:

AF XY:

0.0541

AC XY:

4024

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0155

Gnomad4 AMR

AF:

0.0576

Gnomad4 ASJ

AF:

0.0910

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.110

Gnomad4 FIN

AF:

0.0301

Gnomad4 NFE

AF:

0.0802

Gnomad4 OTH

AF:

0.0650

Alfa

AF:

0.0734

Hom.:

912

Bravo

AF:

0.0531

TwinsUK

AF:

0.0855

AC:

317

ALSPAC

AF:

0.0817

AC:

315

ESP6500AA

AF:

0.0138

AC:

ESP6500EA

AF:

0.0773

AC:

665

ExAC

AF:

0.0655

AC:

7955

Asia WGS

AF:

0.0490

AC:

170

AN:

3478

EpiCase

AF:

0.0781

EpiControl

AF:

0.0812

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 24414483, 24621646, 12023985, 23539294, 19064565, 20004634) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Fanconi anemia complementation group U

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Hereditary cancer-predisposing syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.075

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.71

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

MutationTaster

Benign

0.092

PrimateAI

Benign

0.22

PROVEAN

Benign

0.090

REVEL

Benign

0.030

Sift

Benign

0.37

Sift4G

Benign

0.47

Polyphen

0.047

Vest4

0.029

MPC

0.043

ClinPred

0.0011

GERP RS

1.9

Varity_R

0.027

gMVP

0.27

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over