7-152648641-A-G

Variant names:

• chr7-152648641-A-G
• rs3218539
• NM_005431.2:c.*1T>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005431.2(XRCC2):​c.*1T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00954 in 1,590,890 control chromosomes in the GnomAD database, including 1,223 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (652 hom., cov: 32)
  • Exomes 𝑓: 0.0052 (571 hom.)
• Consequence: XRCC2 NM_005431.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.0180

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 7-152648641-A-G is Benign according to our data. Variant chr7-152648641-A-G is described in ClinVar as [Benign]. Clinvar id is 486724.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC2	NM_005431.2	c.*1T>C		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	ENST00000359321	c.*1T>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_005431.2	ENSP00000352271.1
XRCC2	ENST00000495707.1	n.866T>C		non_coding_transcript_exon_variant	Exon 3 of 3	1
XRCC2	ENST00000698506	c.*1T>C		3_prime_UTR_variant	Exon 2 of 2			ENSP00000513758.1

Frequencies

GnomAD3 genomes AF: 0.0504 AC: 7667 AN: 152156 Hom.: 652 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0211

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0397

GnomAD3 exomes AF: 0.0135 AC: 3102 AN: 230246 Hom.: 238 AF XY: 0.00991 AC XY: 1234 AN XY: 124524

Gnomad AFR exome AF: 0.176

Gnomad AMR exome AF: 0.00766

Gnomad ASJ exome AF: 0.00797

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000193

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000452

Gnomad OTH exome AF: 0.00573

GnomAD4 exome AF: 0.00522 AC: 7505 AN: 1438616 Hom.: 571 Cov.: 31 AF XY: 0.00449 AC XY: 3211 AN XY: 714378

Gnomad4 AFR exome AF: 0.182

Gnomad4 AMR exome AF: 0.00926

Gnomad4 ASJ exome AF: 0.00747

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000343

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000305

Gnomad4 OTH exome AF: 0.00952

GnomAD4 genome AF: 0.0504 AC: 7672 AN: 152274 Hom.: 652 Cov.: 32 AF XY: 0.0489 AC XY: 3638 AN XY: 74468

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.0211

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000470

Gnomad4 OTH AF: 0.0393

Alfa AF: 0.0120 Hom.: 29

Bravo AF: 0.0584

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Apr 02, 2021

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary cancer-predisposing syndrome Benign:1

Aug 18, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	4.6
DANN	Benign	0.82

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

Publications

LitVar

Other links and lift over

dbSNP: rs3218539; hg19: chr7-152345726;