ENST00000495707.1:n.1092_1093delTT

Variant names:

• chr7-152648413-GAA-G
• rs10707642
• ENST00000495707.1:n.1092_1093delTT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000495707.1(XRCC2):​n.1092_1093delTT 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 0.201 in 259,274 control chromosomes in the GnomAD database, including 2,782 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2376 hom., cov: 0)
  • Exomes 𝑓: 0.23 (406 hom.)
• Consequence: XRCC2 ENST00000495707.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.347
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 7-152648413-GAA-G is Benign according to our data. Variant chr7-152648413-GAA-G is described in ClinVar as [Benign]. Clinvar id is 1291098.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC2	NM_005431.2	c.*227_*228delTT		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.1092_1093delTT		non_coding_transcript_exon_variant	Exon 3 of 3	1
XRCC2	ENST00000359321.2	c.*227_*228delTT		3_prime_UTR_variant	Exon 3 of 3	1	NM_005431.2	ENSP00000352271.1
XRCC2	ENST00000698506.1	c.*227_*228delTT		3_prime_UTR_variant	Exon 2 of 2			ENSP00000513758.1
ENSG00000298894	ENST00000758786.1	n.254-12283_254-12282delAA		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.173 AC: 24520 AN: 141400 Hom.: 2376 Cov.: 0

Gnomad AFR AF: 0.0679

Gnomad AMI AF: 0.0516

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.160

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.158

GnomAD4 exome AF: 0.233 AC: 27481 AN: 117846 Hom.: 406 AF XY: 0.234 AC XY: 13706 AN XY: 58602

African (AFR) AF: 0.132 AC: 518 AN: 3936

American (AMR) AF: 0.175 AC: 790 AN: 4522

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 873 AN: 4874

East Asian (EAS) AF: 0.191 AC: 1970 AN: 10336

South Asian (SAS) AF: 0.267 AC: 949 AN: 3554

European-Finnish (FIN) AF: 0.263 AC: 1220 AN: 4636

Middle Eastern (MID) AF: 0.196 AC: 122 AN: 624

European-Non Finnish (NFE) AF: 0.248 AC: 19157 AN: 77236

Other (OTH) AF: 0.232 AC: 1882 AN: 8128

GnomAD4 genome AF: 0.173 AC: 24508 AN: 141428 Hom.: 2376 Cov.: 0 AF XY: 0.173 AC XY: 11794 AN XY: 68354

African (AFR) AF: 0.0679 AC: 2562 AN: 37750

American (AMR) AF: 0.149 AC: 2121 AN: 14192

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 533 AN: 3338

East Asian (EAS) AF: 0.155 AC: 738 AN: 4776

South Asian (SAS) AF: 0.231 AC: 1032 AN: 4458

European-Finnish (FIN) AF: 0.240 AC: 2017 AN: 8388

Middle Eastern (MID) AF: 0.164 AC: 46 AN: 280

European-Non Finnish (NFE) AF: 0.231 AC: 15108 AN: 65432

Other (OTH) AF: 0.158 AC: 306 AN: 1942

Alfa AF: 0.206 Hom.: 839

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 07, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.35
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: rs10707642; hg19: chr7-152345498;