7-152649910-G-A

Variant names:

• chr7-152649910-G-A
• rs3218534
• NM_005431.2:c.122-547C>T

Variant summary

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

The NM_005431.2(XRCC2):​c.122-547C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 152,002 control chromosomes in the GnomAD database, including 12,612 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 0.38 (12612 hom., cov: 32)
• Consequence: XRCC2 NM_005431.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.304
• 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

ENSG00000298894 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.461 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC2	NM_005431.2	MANE Select	c.122-547C>T		intron	N/A	NP_005422.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC2	ENST00000359321.2	TSL:1 MANE Select	c.122-547C>T		intron	N/A	ENSP00000352271.1
	XRCC2	ENST00000495707.1	TSL:1	n.144-547C>T		intron	N/A
	XRCC2	ENST00000698506.1		c.-47-547C>T		intron	N/A	ENSP00000513758.1

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57716 AN: 151882 Hom.: 12613 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.380 AC: 57727 AN: 152002 Hom.: 12612 Cov.: 32 AF XY: 0.386 AC XY: 28684 AN XY: 74280

African (AFR) AF: 0.167 AC: 6931 AN: 41466

American (AMR) AF: 0.383 AC: 5855 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1424 AN: 3472

East Asian (EAS) AF: 0.422 AC: 2175 AN: 5152

South Asian (SAS) AF: 0.358 AC: 1721 AN: 4810

European-Finnish (FIN) AF: 0.613 AC: 6478 AN: 10574

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.465 AC: 31620 AN: 67946

Other (OTH) AF: 0.389 AC: 819 AN: 2108

Alfa AF: 0.409 Hom.: 2031

Bravo AF: 0.355

Asia WGS AF: 0.370 AC: 1292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	0.73
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3218534; hg19: chr7-152346995;