NM_005431.2:c.40-6836_40-6832delCTTTG

Variant names:

• chr7-152667613-TCAAAG-T
• rs3218425
• NM_005431.2:c.40-6836_40-6832delCTTTG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_005431.2(XRCC2):​c.40-6836_40-6832delCTTTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 151,256 control chromosomes in the GnomAD database, including 2,426 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2426 hom., cov: 26)
• Consequence: XRCC2 NM_005431.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 1 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC2	NM_005431.2	MANE Select	c.40-6836_40-6832delCTTTG		intron	N/A	NP_005422.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC2	ENST00000359321.2	TSL:1 MANE Select	c.40-6836_40-6832delCTTTG		intron	N/A	ENSP00000352271.1
	XRCC2	ENST00000698506.1		c.-48+8423_-48+8427delCTTTG		intron	N/A	ENSP00000513758.1
	XRCC2	ENST00000698507.1		n.108-6836_108-6832delCTTTG		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25127 AN: 151142 Hom.: 2425 Cov.: 26

Gnomad AFR AF: 0.0634

Gnomad AMI AF: 0.0496

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.151

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.166 AC: 25119 AN: 151256 Hom.: 2426 Cov.: 26 AF XY: 0.165 AC XY: 12191 AN XY: 73864

African (AFR) AF: 0.0633 AC: 2611 AN: 41222

American (AMR) AF: 0.143 AC: 2170 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 533 AN: 3462

East Asian (EAS) AF: 0.147 AC: 756 AN: 5138

South Asian (SAS) AF: 0.226 AC: 1074 AN: 4746

European-Finnish (FIN) AF: 0.222 AC: 2319 AN: 10456

Middle Eastern (MID) AF: 0.158 AC: 46 AN: 292

European-Non Finnish (NFE) AF: 0.225 AC: 15248 AN: 67776

Other (OTH) AF: 0.151 AC: 317 AN: 2096

Alfa AF: 0.192 Hom.: 360

Bravo AF: 0.155

Asia WGS AF: 0.171 AC: 593 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3218425; hg19: chr7-152364698;