Menu
GeneBe

2-216141316-T-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_021141.4(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
NM_021141.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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_single_submitter, 1 stars. Variant chr2-216141316-T-C is described in Lovd as [Likely_benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.767 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 696 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
XRCC5NM_021141.4 linkuse as main transcriptc.1473T>C p.Phe491= synonymous_variant 13/21 ENST00000392132.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
XRCC5ENST00000392132.7 linkuse as main transcriptc.1473T>C p.Phe491= synonymous_variant 13/211 NM_021141.4 P1
XRCC5ENST00000460284.5 linkuse as main transcriptn.2015T>C non_coding_transcript_exon_variant 10/181
XRCC5ENST00000392133.7 linkuse as main transcriptc.1473T>C p.Phe491= synonymous_variant 15/235 P1
XRCC5ENST00000471649.1 linkuse as main transcriptn.607T>C non_coding_transcript_exon_variant 6/62

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00458
AC:
696
AN:
152130
Hom.:
5
Cov.:
32
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.:
9
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.:
40
Cov.:
31
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00456
AC:
695
AN:
152248
Hom.:
5
Cov.:
32
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.:
3
Bravo
AF:
0.00412
Asia WGS
AF:
0.00318
AC:
11
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 11, 2018- -

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.

Other links and lift over

dbSNP: rs41257924; hg19: chr2-217006039; COSMIC: COSV101079998; API