7-152648459-G-A

Position:

• chr7-152648459-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005431.2(XRCC2):​c.*183C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 485,564 control chromosomes in the GnomAD database, including 1,001 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.060 (827 hom., cov: 32)
  • Exomes 𝑓: 0.011 (174 hom.)
• Consequence: XRCC2 NM_005431.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.605

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 7-152648459-G-A is Benign according to our data. Variant chr7-152648459-G-A is described in ClinVar as [Benign]. Clinvar id is 1272331.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC2	NM_005431.2	c.*183C>T		3_prime_UTR_variant	3/3	ENST00000359321.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC2	ENST00000359321.2	c.*183C>T		3_prime_UTR_variant	3/3	1	NM_005431.2	P1
XRCC2	ENST00000495707.1	n.1048C>T		non_coding_transcript_exon_variant	3/3	1
XRCC2	ENST00000698506.1	c.*183C>T		3_prime_UTR_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.0601 AC: 9053 AN: 150732 Hom.: 827 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0309

Gnomad ASJ AF: 0.0116

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00252

Gnomad FIN AF: 0.00618

Gnomad MID AF: 0.0227

Gnomad NFE AF: 0.00495

Gnomad OTH AF: 0.0513

GnomAD4 exome AF: 0.0105 AC: 3523 AN: 334736 Hom.: 174 Cov.: 6 AF XY: 0.00944 AC XY: 1606 AN XY: 170106

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.0279

Gnomad4 ASJ exome AF: 0.00811

Gnomad4 EAS exome AF: 0.0000424

Gnomad4 SAS exome AF: 0.00278

Gnomad4 FIN exome AF: 0.00830

Gnomad4 NFE exome AF: 0.00425

Gnomad4 OTH exome AF: 0.0175

GnomAD4 genome AF: 0.0601 AC: 9068 AN: 150828 Hom.: 827 Cov.: 32 AF XY: 0.0581 AC XY: 4276 AN XY: 73556

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.0310

Gnomad4 ASJ AF: 0.0116

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.00232

Gnomad4 FIN AF: 0.00618

Gnomad4 NFE AF: 0.00495

Gnomad4 OTH AF: 0.0518

Alfa AF: 0.0119 Hom.: 12

Bravo AF: 0.0690

Asia WGS AF: 0.0210 AC: 72 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.99
DANN	Benign	0.42

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: rs3218541; hg19: chr7-152345544;