Variant chr7-152646717-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_005431.2(XRCC2):c.*1925A>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 0.00863 in 152,248 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0086 ( 8 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

XRCC2
NM_005431.2 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.118

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00863 (1314/152248) while in subpopulation SAS AF= 0.0137 (66/4816). AF 95% confidence interval is 0.0126. There are 8 homozygotes in gnomad4. There are 545 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC2	NM_005431.2 linkuse as main transcript	c.*1925A>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.*1925A>C	3_prime_UTR_variant	3/3	1	NM_005431.2	P1
XRCC2	ENST00000495707.1 linkuse as main transcript	n.2790A>C	non_coding_transcript_exon_variant	3/3	1
XRCC2	ENST00000698506.1 linkuse as main transcript	c.*1925A>C	3_prime_UTR_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.00864

AC:

1315

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00826

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0139

Gnomad FIN

AF:

0.00509

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0133

Gnomad OTH

AF:

0.00860

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

Gnomad4 AFR exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00863

AC:

1314

AN:

152248

Hom.:

Cov.:

AF XY:

0.00732

AC XY:

545

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00323

Gnomad4 AMR

AF:

0.00824

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0137

Gnomad4 FIN

AF:

0.00509

Gnomad4 NFE

AF:

0.0133

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00226

Hom.:

Bravo

AF:

0.00919

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Apr 03, 2015

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.7

DANN

Benign

0.22

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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