rs3218472

chr7-152660792-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_005431.2(XRCC2):c.40-10C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0048 in 1,592,286 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (17 hom., cov: 33)
  • Exomes 𝑓: 0.0042 (27 hom.)
• Consequence: XRCC2 NM_005431.2 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.03597
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.604

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]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 7-152660792-G-A is Benign according to our data. Variant chr7-152660792-G-A is described in ClinVar as [Benign]. Clinvar id is 224934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-152660792-G-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.01 (1529/152306) while in subpopulation AFR AF= 0.0222 (924/41570). AF 95% confidence interval is 0.021. There are 17 homozygotes in gnomad4. There are 712 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC2	NM_005431.2	c.40-10C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000359321.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC2	ENST00000359321.2	c.40-10C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_005431.2	P1
XRCC2	ENST00000495707.1	n.62-10C>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		1
XRCC2	ENST00000698506.1	c.-47-11429C>T		intron_variant
XRCC2	ENST00000698507.1	n.108-10C>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00997 AC: 1518 AN: 152188 Hom.: 16 Cov.: 33

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00956

Gnomad ASJ AF: 0.00662

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00613

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00473

Gnomad OTH AF: 0.0139

GnomAD3 exomes AF: 0.00700 AC: 1671 AN: 238784 Hom.: 9 AF XY: 0.00614 AC XY: 795 AN XY: 129482

Gnomad AFR exome AF: 0.0206

Gnomad AMR exome AF: 0.0198

Gnomad ASJ exome AF: 0.00523

Gnomad EAS exome AF: 0.000114

Gnomad SAS exome AF: 0.00322

Gnomad FIN exome AF: 0.00623

Gnomad NFE exome AF: 0.00387

Gnomad OTH exome AF: 0.00537

GnomAD4 exome AF: 0.00425 AC: 6114 AN: 1439980 Hom.: 27 Cov.: 27 AF XY: 0.00406 AC XY: 2909 AN XY: 717082

Gnomad4 AFR exome AF: 0.0231

Gnomad4 AMR exome AF: 0.0182

Gnomad4 ASJ exome AF: 0.00447

Gnomad4 EAS exome AF: 0.0000506

Gnomad4 SAS exome AF: 0.00301

Gnomad4 FIN exome AF: 0.00722

Gnomad4 NFE exome AF: 0.00319

Gnomad4 OTH exome AF: 0.00495

GnomAD4 genome AF: 0.0100 AC: 1529 AN: 152306 Hom.: 17 Cov.: 33 AF XY: 0.00956 AC XY: 712 AN XY: 74472

Gnomad4 AFR AF: 0.0222

Gnomad4 AMR AF: 0.00968

Gnomad4 ASJ AF: 0.00662

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.00613

Gnomad4 NFE AF: 0.00473

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00776 Hom.: 3

Bravo AF: 0.0110

Asia WGS AF: 0.0140 AC: 50 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Feb 18, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Quest Diagnostics Nichols Institute San Juan Capistrano	May 13, 2021	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Fanconi anemia complementation group U Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
Cadd	Benign	10
Dann	Benign	0.88

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.036
dbscSNV1_RF	Benign	0.34
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

Publications

LitVar

Other links and lift over

dbSNP: rs3218472; hg19: chr7-152357877;