rs3218536

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005431.2(XRCC2):​c.563G>T​(p.Arg188Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

XRCC2
NM_005431.2 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.57
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2946391).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
XRCC2NM_005431.2 linkuse as main transcriptc.563G>T p.Arg188Leu missense_variant 3/3 ENST00000359321.2 NP_005422.1 O43543A0A384MEK2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
XRCC2ENST00000359321.2 linkuse as main transcriptc.563G>T p.Arg188Leu missense_variant 3/31 NM_005431.2 ENSP00000352271.1 O43543
XRCC2ENST00000495707.1 linkuse as main transcriptn.585G>T non_coding_transcript_exon_variant 3/31
XRCC2ENST00000698506.1 linkuse as main transcriptc.395G>T p.Arg132Leu missense_variant 2/2 ENSP00000513758.1 A0A8V8TMB7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461880
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Benign
0.0012
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.29
T
Eigen
Benign
-0.36
Eigen_PC
Benign
-0.32
FATHMM_MKL
Benign
0.75
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.064
D
MetaRNN
Benign
0.29
T
MetaSVM
Benign
-0.82
T
MutationAssessor
Uncertain
2.3
M
PrimateAI
Benign
0.23
T
PROVEAN
Uncertain
-2.8
D
REVEL
Benign
0.20
Sift
Benign
0.058
T
Sift4G
Benign
0.11
T
Polyphen
0.39
B
Vest4
0.43
MutPred
0.44
Loss of catalytic residue at R188 (P = 0.1397);
MVP
0.40
MPC
0.15
ClinPred
0.96
D
GERP RS
1.9
Varity_R
0.12
gMVP
0.45

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs3218536; hg19: chr7-152346007; API