chr7-152648771-C-A

Position:

• chr7-152648771-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_005431.2(XRCC2):​c.714G>T​(p.Arg238Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: XRCC2 NM_005431.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.958

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]

XRCC2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.921

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRCC2	NM_005431.2	c.714G>T	p.Arg238Ser	missense_variant	3/3	ENST00000359321.2	NP_005422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XRCC2	ENST00000359321.2	c.714G>T	p.Arg238Ser	missense_variant	3/3	1	NM_005431.2	ENSP00000352271.1
XRCC2	ENST00000495707.1	n.736G>T		non_coding_transcript_exon_variant	3/3	1
XRCC2	ENST00000698506.1	c.546G>T	p.Arg182Ser	missense_variant	2/2			ENSP00000513758.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.39	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.035	D
MetaRNN	Pathogenic	0.92	D
MetaSVM	Uncertain	-0.090	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.44
Sift	Benign	0.11	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.93
MutPred		0.69		Loss of MoRF binding (P = 0.0469);
MVP		0.52
MPC		0.28
ClinPred		0.99	D
GERP RS		-7.7
Varity_R		0.42
gMVP		0.87

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-152345856;