ENST00000698506.1:c.-174G>C

Variant names:

• chr7-152676167-C-G
• rs3218384
• ENST00000698506.1:c.-174G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000698506.1(XRCC2):​c.-174G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 1,588,906 control chromosomes in the GnomAD database, including 37,420 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2583 hom., cov: 34)
  • Exomes 𝑓: 0.22 (34837 hom.)
• Consequence: XRCC2 ENST00000698506.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.942
• Publications: 30 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 7-152676167-C-G is Benign according to our data. Variant chr7-152676167-C-G is described in ClinVar as Benign. ClinVar VariationId is 1265138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000698506.1. 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.-88G>C		upstream_gene	N/A	NP_005422.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC2	ENST00000698506.1		c.-174G>C		5_prime_UTR	Exon 1 of 2	ENSP00000513758.1
	XRCC2	ENST00000359321.2	TSL:1 MANE Select	c.-88G>C		upstream_gene	N/A	ENSP00000352271.1
	XRCC2	ENST00000698507.1		n.-20G>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26273 AN: 152182 Hom.: 2581 Cov.: 34

Gnomad AFR AF: 0.0829

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.158

GnomAD4 exome AF: 0.216 AC: 310326 AN: 1436604 Hom.: 34837 Cov.: 26 AF XY: 0.217 AC XY: 155513 AN XY: 715512

African (AFR) AF: 0.0782 AC: 2581 AN: 33026

American (AMR) AF: 0.102 AC: 4491 AN: 44178

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 3916 AN: 25876

East Asian (EAS) AF: 0.135 AC: 5311 AN: 39450

South Asian (SAS) AF: 0.234 AC: 20103 AN: 85742

European-Finnish (FIN) AF: 0.224 AC: 11133 AN: 49712

Middle Eastern (MID) AF: 0.167 AC: 953 AN: 5708

European-Non Finnish (NFE) AF: 0.228 AC: 249567 AN: 1093454

Other (OTH) AF: 0.206 AC: 12271 AN: 59458

GnomAD4 genome AF: 0.173 AC: 26280 AN: 152302 Hom.: 2583 Cov.: 34 AF XY: 0.172 AC XY: 12806 AN XY: 74464

African (AFR) AF: 0.0830 AC: 3450 AN: 41578

American (AMR) AF: 0.149 AC: 2277 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 533 AN: 3470

East Asian (EAS) AF: 0.147 AC: 761 AN: 5174

South Asian (SAS) AF: 0.226 AC: 1093 AN: 4832

European-Finnish (FIN) AF: 0.223 AC: 2366 AN: 10622

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15373 AN: 68000

Other (OTH) AF: 0.158 AC: 333 AN: 2114

Alfa AF: 0.113 Hom.: 187

Bravo AF: 0.162

Asia WGS AF: 0.174 AC: 604 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Mar 03, 2015

GeneDx

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	-0.86
CADD	Benign	2.9
DANN	Benign	0.52
PhyloP100		-0.94
PromoterAI		-0.085	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3218384; hg19: chr7-152373252; COSMIC: COSV63771224;