Variant 2-216141316-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The ENST00000392132.7(XRCC5):c.1473T>C(p.Phe491=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00603 in 1,614,050 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0062 ( 40 hom. )

Consequence

XRCC5
ENST00000392132.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.767

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 2-216141316-T-C is Benign according to our data. Variant chr2-216141316-T-C is described in ClinVar as [Benign]. Clinvar id is 775186.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-216141316-T-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.767 with no splicing effect.

BS2

High AC in GnomAd4 at 695 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRCC5	NM_021141.4 linkuse as main transcript	c.1473T>C	p.Phe491=	synonymous_variant	13/21	ENST00000392132.7	NP_066964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
XRCC5	ENST00000392132.7 linkuse as main transcript	c.1473T>C	p.Phe491=	synonymous_variant	13/21	1	NM_021141.4	ENSP00000375977	P1
XRCC5	ENST00000460284.5 linkuse as main transcript	n.2015T>C		non_coding_transcript_exon_variant	10/18	1
XRCC5	ENST00000392133.7 linkuse as main transcript	c.1473T>C	p.Phe491=	synonymous_variant	15/23	5		ENSP00000375978	P1
XRCC5	ENST00000471649.1 linkuse as main transcript	n.607T>C		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes

AF:

0.00458

AC:

696

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00714

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00952

Gnomad FIN

AF:

0.00604

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00572

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00551

AC:

1384

AN:

251326

Hom.:

AF XY:

0.00596

AC XY:

810

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.00336

Gnomad ASJ exome

AF:

0.0154

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00676

Gnomad FIN exome

AF:

0.00656

Gnomad NFE exome

AF:

0.00633

Gnomad OTH exome

AF:

0.00522

GnomAD4 exome

AF:

0.00618

AC:

9035

AN:

1461802

Hom.:

Cov.:

AF XY:

0.00642

AC XY:

4669

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.000926

Gnomad4 AMR exome

AF:

0.00331

Gnomad4 ASJ exome

AF:

0.0138

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00763

Gnomad4 FIN exome

AF:

0.00672

Gnomad4 NFE exome

AF:

0.00638

Gnomad4 OTH exome

AF:

0.00563

GnomAD4 genome

AF:

0.00456

AC:

695

AN:

152248

Hom.:

Cov.:

AF XY:

0.00474

AC XY:

353

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.00706

Gnomad4 ASJ

AF:

0.00980

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00953

Gnomad4 FIN

AF:

0.00604

Gnomad4 NFE

AF:

0.00572

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00593

Hom.:

Bravo

AF:

0.00412

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

6.8

DANN

Benign

0.52

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