NM_005431.2:c.*228dupT

Variant names:

• chr7-152648413-G-GA
• rs10707642
• NM_005431.2:c.*228dupT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_005431.2(XRCC2):​c.*228dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00052 (0 hom., cov: 0)
  • Exomes 𝑓: 0.018 (0 hom.)
• Consequence: XRCC2 NM_005431.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• familial ovarian cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000298894 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000516 (73/141512) while in subpopulation AFR AF = 0.00098 (37/37762). AF 95% confidence interval is 0.00073. There are 0 homozygotes in GnomAd4. There are 38 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005431.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC2	NM_005431.2	MANE Select	c.*228dupT		3_prime_UTR	Exon 3 of 3	NP_005422.1	O43543

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC2	ENST00000359321.2	TSL:1 MANE Select	c.*228dupT		3_prime_UTR	Exon 3 of 3	ENSP00000352271.1	O43543
	XRCC2	ENST00000495707.1	TSL:1	n.1093dupT		non_coding_transcript_exon	Exon 3 of 3
	XRCC2	ENST00000698506.1		c.*228dupT		3_prime_UTR	Exon 2 of 2	ENSP00000513758.1	A0A8V8TMB7

Frequencies

GnomAD3 genomes AF: 0.000509 AC: 72 AN: 141484 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000955

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000141

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000417

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000357

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000443

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0184 AC: 2177 AN: 118306 Hom.: 0 Cov.: 0 AF XY: 0.0187 AC XY: 1097 AN XY: 58816

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0223 AC: 88 AN: 3954

American (AMR) AF: 0.0208 AC: 94 AN: 4514

Ashkenazi Jewish (ASJ) AF: 0.0295 AC: 145 AN: 4910

East Asian (EAS) AF: 0.0103 AC: 108 AN: 10436

South Asian (SAS) AF: 0.0146 AC: 52 AN: 3558

European-Finnish (FIN) AF: 0.0138 AC: 64 AN: 4632

Middle Eastern (MID) AF: 0.0241 AC: 15 AN: 622

European-Non Finnish (NFE) AF: 0.0185 AC: 1435 AN: 77524

Other (OTH) AF: 0.0216 AC: 176 AN: 8156

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000516 AC: 73 AN: 141512 Hom.: 0 Cov.: 0 AF XY: 0.000555 AC XY: 38 AN XY: 68408

African (AFR) AF: 0.000980 AC: 37 AN: 37762

American (AMR) AF: 0.000141 AC: 2 AN: 14204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3340

East Asian (EAS) AF: 0.000418 AC: 2 AN: 4780

South Asian (SAS) AF: 0.00 AC: 0 AN: 4466

European-Finnish (FIN) AF: 0.000357 AC: 3 AN: 8396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.000443 AC: 29 AN: 65466

Other (OTH) AF: 0.00 AC: 0 AN: 1946

Alfa AF: 0.000665 Hom.: 839

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.34

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;