rs3218417

Variant names:

• chr7-152668549-AC-A
• rs3218417
• NM_005431.2:c.39+7491delG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_005431.2(XRCC2):​c.39+7491delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,058 control chromosomes in the GnomAD database, including 5,206 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (5206 hom., cov: 21)
• Consequence: XRCC2 NM_005431.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355
• Publications: 3 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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC2	NM_005431.2	c.39+7491delG		intron_variant	Intron 1 of 2	ENST00000359321.2	NP_005422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC2	ENST00000359321.2	c.39+7491delG		intron_variant	Intron 1 of 2	1	NM_005431.2	ENSP00000352271.1
XRCC2	ENST00000698506.1	c.-48+7491delG		intron_variant	Intron 1 of 1			ENSP00000513758.1
XRCC2	ENST00000698507.1	n.107+7491delG		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39389 AN: 151940 Hom.: 5200 Cov.: 21

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.0694

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.259 AC: 39415 AN: 152058 Hom.: 5206 Cov.: 21 AF XY: 0.258 AC XY: 19196 AN XY: 74314

African (AFR) AF: 0.283 AC: 11722 AN: 41480

American (AMR) AF: 0.200 AC: 3045 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 703 AN: 3470

East Asian (EAS) AF: 0.275 AC: 1421 AN: 5162

South Asian (SAS) AF: 0.319 AC: 1538 AN: 4822

European-Finnish (FIN) AF: 0.246 AC: 2603 AN: 10582

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17752 AN: 67980

Other (OTH) AF: 0.234 AC: 495 AN: 2112

Alfa AF: 0.254 Hom.: 594

Bravo AF: 0.255

Asia WGS AF: 0.272 AC: 943 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.35
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: rs3218417; hg19: chr7-152365634;