7-152665780-C-G

Variant names:

• chr7-152665780-C-G
• rs3094406
• NM_005431.2:c.40-4998G>C

Variant summary

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

The NM_005431.2(XRCC2):​c.40-4998G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.852 in 152,054 control chromosomes in the GnomAD database, including 55,571 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 0.85 (55571 hom., cov: 31)
• Consequence: XRCC2 NM_005431.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.290
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC2	NM_005431.2	c.40-4998G>C		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.40-4998G>C		intron_variant	Intron 1 of 2	1	NM_005431.2	ENSP00000352271.1
XRCC2	ENST00000698506.1	c.-48+10261G>C		intron_variant	Intron 1 of 1			ENSP00000513758.1
XRCC2	ENST00000698507.1	n.108-4998G>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.852 AC: 129417 AN: 151934 Hom.: 55543 Cov.: 31

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.702

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.964

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.908

Gnomad OTH AF: 0.837

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

GnomAD4 genome AF: 0.852 AC: 129495 AN: 152054 Hom.: 55571 Cov.: 31 AF XY: 0.851 AC XY: 63297 AN XY: 74352

African (AFR) AF: 0.792 AC: 32827 AN: 41454

American (AMR) AF: 0.748 AC: 11421 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 2886 AN: 3468

East Asian (EAS) AF: 0.702 AC: 3619 AN: 5154

South Asian (SAS) AF: 0.837 AC: 4034 AN: 4822

European-Finnish (FIN) AF: 0.964 AC: 10211 AN: 10592

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.908 AC: 61762 AN: 67996

Other (OTH) AF: 0.834 AC: 1754 AN: 2104

Alfa AF: 0.874 Hom.: 6825

Bravo AF: 0.830

Asia WGS AF: 0.745 AC: 2584 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	1.9
DANN	Benign	0.91
PhyloP100		0.29
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: rs3094406; hg19: chr7-152362865;