Variant chr2-216148178-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_021141.4(XRCC5):c.1572A>G(p.Thr524=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 1,613,894 control chromosomes in the GnomAD database, including 619,911 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.88 ( 58474 hom., cov: 31)

Exomes 𝑓: 0.88 ( 561437 hom. )

Consequence

XRCC5
NM_021141.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.335

Variant links:

Genes affected

XRCC5 (HGNC:12833): (X-ray repair cross complementing 5) The protein encoded by this gene is the 80-kilodalton subunit of the Ku heterodimer protein which is also known as ATP-dependant DNA helicase II or DNA repair protein XRCC5. Ku is the DNA-binding component of the DNA-dependent protein kinase, and it functions together with the DNA ligase IV-XRCC4 complex in the repair of DNA double-strand break by non-homologous end joining and the completion of V(D)J recombination events. This gene functionally complements Chinese hamster xrs-6, a mutant defective in DNA double-strand break repair and in ability to undergo V(D)J recombination. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. [provided by RefSeq, Jul 2008]

XRCC5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP7

Synonymous conserved (PhyloP=-0.335 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC5	NM_021141.4 linkuse as main transcript	c.1572A>G	p.Thr524=	synonymous_variant	14/21	ENST00000392132.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
XRCC5	ENST00000392132.7 linkuse as main transcript	c.1572A>G	p.Thr524=	synonymous_variant	14/21	1	NM_021141.4	P1
XRCC5	ENST00000460284.5 linkuse as main transcript	n.2114A>G		non_coding_transcript_exon_variant	11/18	1
XRCC5	ENST00000392133.7 linkuse as main transcript	c.1572A>G	p.Thr524=	synonymous_variant	16/23	5		P1

Frequencies

GnomAD3 genomes

AF:

0.876

AC:

133245

AN:

152116

Hom.:

58430

Cov.:

show subpopulations

Gnomad AFR

AF:

0.874

Gnomad AMI

AF:

0.699

Gnomad AMR

AF:

0.892

Gnomad ASJ

AF:

0.872

Gnomad EAS

AF:

0.917

Gnomad SAS

AF:

0.816

Gnomad FIN

AF:

0.929

Gnomad MID

AF:

0.899

Gnomad NFE

AF:

0.869

Gnomad OTH

AF:

0.889

GnomAD3 exomes

AF:

0.876

AC:

220009

AN:

251124

Hom.:

96566

AF XY:

0.872

AC XY:

118394

AN XY:

135720

show subpopulations

Gnomad AFR exome

AF:

0.879

Gnomad AMR exome

AF:

0.892

Gnomad ASJ exome

AF:

0.880

Gnomad EAS exome

AF:

0.922

Gnomad SAS exome

AF:

0.819

Gnomad FIN exome

AF:

0.922

Gnomad NFE exome

AF:

0.870

Gnomad OTH exome

AF:

0.875

GnomAD4 exome

AF:

0.876

AC:

1280592

AN:

1461660

Hom.:

561437

Cov.:

AF XY:

0.874

AC XY:

635238

AN XY:

727140

show subpopulations

Gnomad4 AFR exome

AF:

0.876

Gnomad4 AMR exome

AF:

0.893

Gnomad4 ASJ exome

AF:

0.878

Gnomad4 EAS exome

AF:

0.918

Gnomad4 SAS exome

AF:

0.817

Gnomad4 FIN exome

AF:

0.919

Gnomad4 NFE exome

AF:

0.876

Gnomad4 OTH exome

AF:

0.878

GnomAD4 genome

AF:

0.876

AC:

133347

AN:

152234

Hom.:

58474

Cov.:

AF XY:

0.877

AC XY:

65286

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.874

Gnomad4 AMR

AF:

0.891

Gnomad4 ASJ

AF:

0.872

Gnomad4 EAS

AF:

0.916

Gnomad4 SAS

AF:

0.816

Gnomad4 FIN

AF:

0.929

Gnomad4 NFE

AF:

0.869

Gnomad4 OTH

AF:

0.890

Alfa

AF:

0.869

Hom.:

93577

Bravo

AF:

0.877

Asia WGS

AF:

0.859

AC:

2991

AN:

3478

EpiCase

AF:

0.860

EpiControl

AF:

0.864

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.43

DANN

Benign

0.36

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over