7-152665390-A-G

Variant names:

• chr7-152665390-A-G
• rs3111465
• NM_005431.2:c.40-4608T>C

Variant summary

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

The NM_005431.2(XRCC2):​c.40-4608T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.947 in 151,966 control chromosomes in the GnomAD database, including 68,201 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 0.95 (68201 hom., cov: 29)
• Consequence: XRCC2 NM_005431.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.543
• 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC2	NM_005431.2	c.40-4608T>C		intron_variant	Intron 1 of 2	ENST00000359321.2	NP_005422.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC2	ENST00000359321.2	c.40-4608T>C		intron_variant	Intron 1 of 2	1	NM_005431.2	ENSP00000352271.1
XRCC2	ENST00000698506.1	c.-48+10651T>C		intron_variant	Intron 1 of 1			ENSP00000513758.1
XRCC2	ENST00000698507.1	n.108-4608T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.947 AC: 143801 AN: 151848 Hom.: 68144 Cov.: 29

Gnomad AFR AF: 0.933

Gnomad AMI AF: 0.915

Gnomad AMR AF: 0.956

Gnomad ASJ AF: 0.941

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.947

Gnomad FIN AF: 0.984

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.954

Gnomad OTH AF: 0.944

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

GnomAD4 genome AF: 0.947 AC: 143914 AN: 151966 Hom.: 68201 Cov.: 29 AF XY: 0.948 AC XY: 70391 AN XY: 74258

African (AFR) AF: 0.933 AC: 38671 AN: 41448

American (AMR) AF: 0.956 AC: 14549 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.941 AC: 3262 AN: 3468

East Asian (EAS) AF: 0.875 AC: 4517 AN: 5162

South Asian (SAS) AF: 0.947 AC: 4552 AN: 4808

European-Finnish (FIN) AF: 0.984 AC: 10384 AN: 10556

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.954 AC: 64882 AN: 67990

Other (OTH) AF: 0.942 AC: 1987 AN: 2110

Alfa AF: 0.949 Hom.: 9161

Bravo AF: 0.943

Asia WGS AF: 0.911 AC: 3170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.4
DANN	Benign	0.81
PhyloP100		-0.54
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: rs3111465; hg19: chr7-152362475;