Variant chr2-216130957-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_021141.4(XRCC5):c.1020C>T(p.Phe340=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,613,304 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 6 hom. )

Consequence

XRCC5
NM_021141.4 synonymous

Scores

Clinical Significance

Benign/Likely benign no assertion criteria provided B:2

Conservation

PhyloP100: 0.794

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 2-216130957-C-T is Benign according to our data. Variant chr2-216130957-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1285048.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-216130957-C-T is described in Lovd as [Benign]. Variant chr2-216130957-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.794 with no splicing effect.

BS2

High AC in GnomAd4 at 192 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC5	NM_021141.4 linkuse as main transcript	c.1020C>T	p.Phe340=	synonymous_variant	9/21	ENST00000392132.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
XRCC5	ENST00000392132.7 linkuse as main transcript	c.1020C>T	p.Phe340=	synonymous_variant	9/21	1	NM_021141.4	P1
XRCC5	ENST00000460284.5 linkuse as main transcript	n.1562C>T		non_coding_transcript_exon_variant	6/18	1
XRCC5	ENST00000392133.7 linkuse as main transcript	c.1020C>T	p.Phe340=	synonymous_variant	11/23	5		P1
XRCC5	ENST00000471649.1 linkuse as main transcript	n.154C>T		non_coding_transcript_exon_variant	2/6	2

Frequencies

GnomAD3 genomes

AF:

0.00126

AC:

192

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00215

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00145

AC:

363

AN:

250524

Hom.:

AF XY:

0.00148

AC XY:

201

AN XY:

135436

show subpopulations

Gnomad AFR exome

AF:

0.000432

Gnomad AMR exome

AF:

0.00196

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00144

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00195

Gnomad OTH exome

AF:

0.00329

GnomAD4 exome

AF:

0.00198

AC:

2890

AN:

1461012

Hom.:

Cov.:

AF XY:

0.00199

AC XY:

1450

AN XY:

726828

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.00166

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00224

Gnomad4 FIN exome

AF:

0.000656

Gnomad4 NFE exome

AF:

0.00223

Gnomad4 OTH exome

AF:

0.00151

GnomAD4 genome

AF:

0.00126

AC:

192

AN:

152292

Hom.:

Cov.:

AF XY:

0.00125

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00215

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00128

Hom.:

Bravo

AF:

0.00122

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00147

EpiControl

AF:

0.00237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

- -

not provided

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.70

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