Variant 7-152648641-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005431.2(XRCC2):c.*1T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00954 in 1,590,890 control chromosomes in the GnomAD database, including 1,223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 652 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 571 hom. )

Consequence

XRCC2
NM_005431.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0180

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 (BayesDel_noAF=-0.66).

BP6

Variant 7-152648641-A-G is Benign according to our data. Variant chr7-152648641-A-G is described in ClinVar as [Benign]. Clinvar id is 486724.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC2	NM_005431.2 linkuse as main transcript	c.*1T>C		3_prime_UTR_variant	3/3	ENST00000359321.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
XRCC2	ENST00000359321.2 linkuse as main transcript	c.*1T>C	3_prime_UTR_variant	3/3	1	NM_005431.2	P1
XRCC2	ENST00000495707.1 linkuse as main transcript	n.866T>C	non_coding_transcript_exon_variant	3/3	1
XRCC2	ENST00000698506.1 linkuse as main transcript	c.*1T>C	3_prime_UTR_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.0504

AC:

7667

AN:

152156

Hom.:

652

Cov.:

show subpopulations

Gnomad AFR

AF:

0.174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0211

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.0397

GnomAD3 exomes

AF:

0.0135

AC:

3102

AN:

230246

Hom.:

238

AF XY:

0.00991

AC XY:

1234

AN XY:

124524

show subpopulations

Gnomad AFR exome

AF:

0.176

Gnomad AMR exome

AF:

0.00766

Gnomad ASJ exome

AF:

0.00797

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000193

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000452

Gnomad OTH exome

AF:

0.00573

GnomAD4 exome

AF:

0.00522

AC:

7505

AN:

1438616

Hom.:

571

Cov.:

AF XY:

0.00449

AC XY:

3211

AN XY:

714378

show subpopulations

Gnomad4 AFR exome

AF:

0.182

Gnomad4 AMR exome

AF:

0.00926

Gnomad4 ASJ exome

AF:

0.00747

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000343

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000305

Gnomad4 OTH exome

AF:

0.00952

GnomAD4 genome

AF:

0.0504

AC:

7672

AN:

152274

Hom.:

652

Cov.:

AF XY:

0.0489

AC XY:

3638

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.173

Gnomad4 AMR

AF:

0.0211

Gnomad4 ASJ

AF:

0.00922

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000470

Gnomad4 OTH

AF:

0.0393

Alfa

AF:

0.0120

Hom.:

Bravo

AF:

0.0584

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Quest Diagnostics Nichols Institute San Juan Capistrano

Apr 02, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Hereditary cancer-predisposing syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 18, 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

BayesDel_noAF

Benign

-0.66

Cadd

Benign

4.6

Dann

Benign

0.82

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