rs3218385

Variant names:

• chr7-152676148-A-C
• rs3218385
• ENST00000698506.1:c.-155T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-152676148-A-C
• chr7-152676148-A-G

Variant summary

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

The ENST00000698506.1(XRCC2):​c.-155T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0498 in 1,607,010 control chromosomes in the GnomAD database, including 2,345 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 0.062 (365 hom., cov: 33)
  • Exomes 𝑓: 0.048 (1980 hom.)
• Consequence: XRCC2 ENST00000698506.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.33
• Publications: 12 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC2	NM_005431.2	c.-69T>G		upstream_gene_variant		ENST00000359321.2	NP_005422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC2	ENST00000698506.1	c.-155T>G		5_prime_UTR_variant	Exon 1 of 2			ENSP00000513758.1
XRCC2	ENST00000359321.2	c.-69T>G		upstream_gene_variant		1	NM_005431.2	ENSP00000352271.1
XRCC2	ENST00000698507.1	n.-1T>G		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0621 AC: 9422 AN: 151844 Hom.: 359 Cov.: 33

Gnomad AFR AF: 0.0980

Gnomad AMI AF: 0.0870

Gnomad AMR AF: 0.0484

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.0550

Gnomad FIN AF: 0.0163

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0458

Gnomad OTH AF: 0.0628

GnomAD4 exome AF: 0.0485 AC: 70568 AN: 1455050 Hom.: 1980 Cov.: 29 AF XY: 0.0488 AC XY: 35324 AN XY: 724238

African (AFR) AF: 0.0971 AC: 3234 AN: 33316

American (AMR) AF: 0.0451 AC: 2013 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.0592 AC: 1542 AN: 26040

East Asian (EAS) AF: 0.0885 AC: 3509 AN: 39640

South Asian (SAS) AF: 0.0528 AC: 4544 AN: 86138

European-Finnish (FIN) AF: 0.0178 AC: 928 AN: 52078

Middle Eastern (MID) AF: 0.0617 AC: 355 AN: 5752

European-Non Finnish (NFE) AF: 0.0462 AC: 51122 AN: 1107294

Other (OTH) AF: 0.0552 AC: 3321 AN: 60128

GnomAD4 genome AF: 0.0621 AC: 9438 AN: 151960 Hom.: 365 Cov.: 33 AF XY: 0.0610 AC XY: 4531 AN XY: 74274

African (AFR) AF: 0.0981 AC: 4066 AN: 41432

American (AMR) AF: 0.0481 AC: 735 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0599 AC: 208 AN: 3470

East Asian (EAS) AF: 0.125 AC: 644 AN: 5142

South Asian (SAS) AF: 0.0548 AC: 264 AN: 4816

European-Finnish (FIN) AF: 0.0163 AC: 172 AN: 10576

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0459 AC: 3115 AN: 67934

Other (OTH) AF: 0.0650 AC: 137 AN: 2108

Alfa AF: 0.0548 Hom.: 201

Bravo AF: 0.0673

Asia WGS AF: 0.0890 AC: 310 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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.3
DANN	Benign	0.44
PhyloP100		-1.3
PromoterAI		-0.0019	Neutral
Mutation Taster		=300/0	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: rs3218385; hg19: chr7-152373233; COSMIC: COSV63770221;