7-152648413-GA-G

Variant names:

• chr7-152648413-GA-G
• rs10707642
• ENST00000495707.1:n.1093delT

Variant summary

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

The NM_005431.2(XRCC2):​c.*228delT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.69 (33165 hom., cov: 0)
  • Exomes 𝑓: 0.44 (1060 hom.)
• Consequence: XRCC2 NM_005431.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.345
• 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-GA-G is Benign according to our data. Variant chr7-152648413-GA-G is described in ClinVar as [Benign]. Clinvar id is 1181545.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC2	NM_005431.2	c.*228delT		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.1093delT		non_coding_transcript_exon_variant	Exon 3 of 3	1
XRCC2	ENST00000359321.2	c.*228delT		3_prime_UTR_variant	Exon 3 of 3	1	NM_005431.2	ENSP00000352271.1
XRCC2	ENST00000698506.1	c.*228delT		3_prime_UTR_variant	Exon 2 of 2			ENSP00000513758.1
ENSG00000298894	ENST00000758786.1	n.254-12282delA		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.687 AC: 97196 AN: 141428 Hom.: 33158 Cov.: 0

Gnomad AFR AF: 0.780

Gnomad AMI AF: 0.841

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.660

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.705

GnomAD4 exome AF: 0.441 AC: 52055 AN: 118074 Hom.: 1060 Cov.: 0 AF XY: 0.440 AC XY: 25796 AN XY: 58672

African (AFR) AF: 0.468 AC: 1861 AN: 3978

American (AMR) AF: 0.467 AC: 2129 AN: 4558

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 2172 AN: 4900

East Asian (EAS) AF: 0.478 AC: 5021 AN: 10512

South Asian (SAS) AF: 0.440 AC: 1557 AN: 3536

European-Finnish (FIN) AF: 0.451 AC: 2087 AN: 4628

Middle Eastern (MID) AF: 0.442 AC: 277 AN: 626

European-Non Finnish (NFE) AF: 0.432 AC: 33375 AN: 77184

Other (OTH) AF: 0.439 AC: 3576 AN: 8152

GnomAD4 genome AF: 0.687 AC: 97219 AN: 141456 Hom.: 33165 Cov.: 0 AF XY: 0.691 AC XY: 47229 AN XY: 68378

African (AFR) AF: 0.780 AC: 29424 AN: 37742

American (AMR) AF: 0.734 AC: 10418 AN: 14192

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2201 AN: 3338

East Asian (EAS) AF: 0.717 AC: 3429 AN: 4780

South Asian (SAS) AF: 0.669 AC: 2983 AN: 4456

European-Finnish (FIN) AF: 0.657 AC: 5523 AN: 8400

Middle Eastern (MID) AF: 0.646 AC: 181 AN: 280

European-Non Finnish (NFE) AF: 0.626 AC: 40956 AN: 65450

Other (OTH) AF: 0.705 AC: 1371 AN: 1946

Alfa AF: 0.576 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.34
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;