ENST00000495707.1:n.1048C>T

Variant names:

• chr7-152648459-G-A
• rs3218541
• ENST00000495707.1:n.1048C>T

Variant summary

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

The ENST00000495707.1(XRCC2):​n.1048C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 485,564 control chromosomes in the GnomAD database, including 1,001 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 0.060 (827 hom., cov: 32)
  • Exomes 𝑓: 0.011 (174 hom.)
• Consequence: XRCC2 ENST00000495707.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.605
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC2	NM_005431.2	c.*183C>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000359321.2	NP_005422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC2	ENST00000495707.1	n.1048C>T		non_coding_transcript_exon_variant	Exon 3 of 3	1
XRCC2	ENST00000359321.2	c.*183C>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_005431.2	ENSP00000352271.1
XRCC2	ENST00000698506.1	c.*183C>T		3_prime_UTR_variant	Exon 2 of 2			ENSP00000513758.1
ENSG00000298894	ENST00000758786.1	n.254-12251G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0601 AC: 9053 AN: 150732 Hom.: 827 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0309

Gnomad ASJ AF: 0.0116

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00252

Gnomad FIN AF: 0.00618

Gnomad MID AF: 0.0227

Gnomad NFE AF: 0.00495

Gnomad OTH AF: 0.0513

GnomAD4 exome AF: 0.0105 AC: 3523 AN: 334736 Hom.: 174 Cov.: 6 AF XY: 0.00944 AC XY: 1606 AN XY: 170106

African (AFR) AF: 0.190 AC: 1637 AN: 8614

American (AMR) AF: 0.0279 AC: 278 AN: 9958

Ashkenazi Jewish (ASJ) AF: 0.00811 AC: 81 AN: 9988

East Asian (EAS) AF: 0.0000424 AC: 1 AN: 23580

South Asian (SAS) AF: 0.00278 AC: 32 AN: 11522

European-Finnish (FIN) AF: 0.00830 AC: 172 AN: 20722

Middle Eastern (MID) AF: 0.00690 AC: 10 AN: 1450

European-Non Finnish (NFE) AF: 0.00425 AC: 975 AN: 229654

Other (OTH) AF: 0.0175 AC: 337 AN: 19248

GnomAD4 genome AF: 0.0601 AC: 9068 AN: 150828 Hom.: 827 Cov.: 32 AF XY: 0.0581 AC XY: 4276 AN XY: 73556

African (AFR) AF: 0.196 AC: 8035 AN: 41044

American (AMR) AF: 0.0310 AC: 467 AN: 15082

Ashkenazi Jewish (ASJ) AF: 0.0116 AC: 40 AN: 3460

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5138

South Asian (SAS) AF: 0.00232 AC: 11 AN: 4746

European-Finnish (FIN) AF: 0.00618 AC: 63 AN: 10188

Middle Eastern (MID) AF: 0.0243 AC: 7 AN: 288

European-Non Finnish (NFE) AF: 0.00495 AC: 336 AN: 67886

Other (OTH) AF: 0.0518 AC: 108 AN: 2086

Alfa AF: 0.0190 Hom.: 29

Bravo AF: 0.0690

Asia WGS AF: 0.0210 AC: 72 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 23, 2018

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	-0.94
CADD	Benign	0.99
DANN	Benign	0.42
PhyloP100		-0.60
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: rs3218541; hg19: chr7-152345544;