NM_005431.2:c.40-10C>T

Variant names:

• chr7-152660792-G-A
• rs3218472
• NM_005431.2:c.40-10C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_005431.2(XRCC2):​c.40-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0048 in 1,592,286 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (17 hom., cov: 33)
  • Exomes 𝑓: 0.0042 (27 hom.)
• Consequence: XRCC2 NM_005431.2 intron
• Scores: Splicing: ADA: 0.03597
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.604
• Publications: 6 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 7-152660792-G-A is Benign according to our data. Variant chr7-152660792-G-A is described in ClinVar as Benign. ClinVar VariationId is 224934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.01 (1529/152306) while in subpopulation AFR AF = 0.0222 (924/41570). AF 95% confidence interval is 0.021. There are 17 homozygotes in GnomAd4. There are 712 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 17 AD,AR,Unknown gene

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.40-10C>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.40-10C>T		intron	N/A	ENSP00000352271.1
	XRCC2	ENST00000495707.1	TSL:1	n.62-10C>T		intron	N/A
	ENSG00000298894	ENST00000758786.1		n.336G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.00997 AC: 1518 AN: 152188 Hom.: 16 Cov.: 33

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00956

Gnomad ASJ AF: 0.00662

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00613

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00473

Gnomad OTH AF: 0.0139

GnomAD2 exomes AF: 0.00700 AC: 1671 AN: 238784 AF XY: 0.00614

Gnomad AFR exome AF: 0.0206

Gnomad AMR exome AF: 0.0198

Gnomad ASJ exome AF: 0.00523

Gnomad EAS exome AF: 0.000114

Gnomad FIN exome AF: 0.00623

Gnomad NFE exome AF: 0.00387

Gnomad OTH exome AF: 0.00537

GnomAD4 exome AF: 0.00425 AC: 6114 AN: 1439980 Hom.: 27 Cov.: 27 AF XY: 0.00406 AC XY: 2909 AN XY: 717082

African (AFR) AF: 0.0231 AC: 749 AN: 32454

American (AMR) AF: 0.0182 AC: 762 AN: 41832

Ashkenazi Jewish (ASJ) AF: 0.00447 AC: 115 AN: 25720

East Asian (EAS) AF: 0.0000506 AC: 2 AN: 39564

South Asian (SAS) AF: 0.00301 AC: 252 AN: 83610

European-Finnish (FIN) AF: 0.00722 AC: 378 AN: 52360

Middle Eastern (MID) AF: 0.00987 AC: 56 AN: 5672

European-Non Finnish (NFE) AF: 0.00319 AC: 3505 AN: 1099226

Other (OTH) AF: 0.00495 AC: 295 AN: 59542

GnomAD4 genome AF: 0.0100 AC: 1529 AN: 152306 Hom.: 17 Cov.: 33 AF XY: 0.00956 AC XY: 712 AN XY: 74472

African (AFR) AF: 0.0222 AC: 924 AN: 41570

American (AMR) AF: 0.00968 AC: 148 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00662 AC: 23 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4830

European-Finnish (FIN) AF: 0.00613 AC: 65 AN: 10608

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00473 AC: 322 AN: 68028

Other (OTH) AF: 0.0147 AC: 31 AN: 2110

Alfa AF: 0.00819 Hom.: 4

Bravo AF: 0.0110

Asia WGS AF: 0.0140 AC: 50 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

not specified Benign:2

May 13, 2021

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 18, 2021

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Fanconi anemia complementation group U Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	10
DANN	Benign	0.88
PhyloP100		0.60
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.036
dbscSNV1_RF	Benign	0.34
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: rs3218472; hg19: chr7-152357877;