rs3218493

Variant names:

• chr7-152656578-G-C
• rs3218493
• NM_005431.2:c.121+4123C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005431.2(XRCC2):​c.121+4123C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0618 in 147,996 control chromosomes in the GnomAD database, including 572 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.062 (572 hom., cov: 32)
• Consequence: XRCC2 NM_005431.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 4 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, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• familial ovarian cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000298894 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC2	NM_005431.2	MANE Select	c.121+4123C>G		intron	N/A	NP_005422.1	O43543

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC2	ENST00000359321.2	TSL:1 MANE Select	c.121+4123C>G		intron	N/A	ENSP00000352271.1	O43543
	XRCC2	ENST00000495707.1	TSL:1	n.143+4123C>G		intron	N/A
	XRCC2	ENST00000698506.1		c.-47-7215C>G		intron	N/A	ENSP00000513758.1	A0A8V8TMB7

Frequencies

GnomAD3 genomes AF: 0.0617 AC: 9131 AN: 147874 Hom.: 568 Cov.: 32

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0223

Gnomad MID AF: 0.0645

Gnomad NFE AF: 0.0462

Gnomad OTH AF: 0.0864

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0618 AC: 9146 AN: 147996 Hom.: 572 Cov.: 32 AF XY: 0.0653 AC XY: 4695 AN XY: 71942

African (AFR) AF: 0.0198 AC: 816 AN: 41264

American (AMR) AF: 0.202 AC: 2961 AN: 14628

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 355 AN: 3432

East Asian (EAS) AF: 0.181 AC: 901 AN: 4990

South Asian (SAS) AF: 0.114 AC: 527 AN: 4618

European-Finnish (FIN) AF: 0.0223 AC: 211 AN: 9458

Middle Eastern (MID) AF: 0.0552 AC: 16 AN: 290

European-Non Finnish (NFE) AF: 0.0462 AC: 3072 AN: 66422

Other (OTH) AF: 0.0879 AC: 178 AN: 2026

Alfa AF: 0.0515 Hom.: 42

Bravo AF: 0.0731

Asia WGS AF: 0.154 AC: 534 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.63
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs3218493; hg19: chr7-152353663;