chr7-152669999-T-C

Variant names:

• chr7-152669999-T-C
• rs3218410
• NM_005431.2:c.39+6042A>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.39+6042A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 151,806 control chromosomes in the GnomAD database, including 2,685 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 0.18 (2685 hom., cov: 31)
• Consequence: XRCC2 NM_005431.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC2	NM_005431.2	c.39+6042A>G		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+6042A>G		intron_variant	Intron 1 of 2	1	NM_005431.2	ENSP00000352271.1
XRCC2	ENST00000698506.1	c.-48+6042A>G		intron_variant	Intron 1 of 1			ENSP00000513758.1
XRCC2	ENST00000698507.1	n.107+6042A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27542 AN: 151694 Hom.: 2681 Cov.: 31

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0495

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.182 AC: 27558 AN: 151806 Hom.: 2685 Cov.: 31 AF XY: 0.181 AC XY: 13404 AN XY: 74168

African (AFR) AF: 0.113 AC: 4703 AN: 41470

American (AMR) AF: 0.153 AC: 2327 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 535 AN: 3472

East Asian (EAS) AF: 0.148 AC: 752 AN: 5084

South Asian (SAS) AF: 0.228 AC: 1095 AN: 4802

European-Finnish (FIN) AF: 0.223 AC: 2344 AN: 10526

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.226 AC: 15361 AN: 67900

Other (OTH) AF: 0.165 AC: 348 AN: 2108

Alfa AF: 0.197 Hom.: 1111

Bravo AF: 0.173

Asia WGS AF: 0.175 AC: 609 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.4
DANN	Benign	0.43
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: rs3218410; hg19: chr7-152367084;