rs534746330

Variant names:

• chr7-152648771-C-A
• rs534746330
• NM_005431.2:c.714G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-152648771-C-A
• chr7-152648771-C-G
• chr7-152648771-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R238K) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: XRCC2 NM_005431.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.958
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group U

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• premature ovarian failure 17

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• spermatogenic failure 50

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
• breast cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics
• familial ovarian cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000298894 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005431.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC2	NM_005431.2	MANE Select	c.714G>T	p.Arg238Ser	missense	Exon 3 of 3	NP_005422.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC2	ENST00000359321.2	TSL:1 MANE Select	c.714G>T	p.Arg238Ser	missense	Exon 3 of 3	ENSP00000352271.1
	XRCC2	ENST00000495707.1	TSL:1	n.736G>T		non_coding_transcript_exon	Exon 3 of 3
	XRCC2	ENST00000698506.1		c.546G>T	p.Arg182Ser	missense	Exon 2 of 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 v4.9

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
PhyloP100		-0.96
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
Mutation Taster		=53/47	polymorphism

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

Other links and lift over

dbSNP: rs534746330; hg19: chr7-152345856;