rs10786737

Positions:

• chr10-103097461-A-C
• chr10-103097461-A-G

Variant summary

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

The NM_001351169.2(NT5C2):​c.688-87T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 1,120,990 control chromosomes in the GnomAD database, including 14,275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1771 hom., cov: 32)
  • Exomes 𝑓: 0.16 (12504 hom.)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0780

Genes affected

NT5C2 (HGNC:8022): (5'-nucleotidase, cytosolic II) This gene encodes a hydrolase that serves as an important role in cellular purine metabolism by acting primarily on inosine 5'-monophosphate and other purine nucleotides. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-103097461-A-C is Benign according to our data. Variant chr10-103097461-A-C is described in ClinVar as [Benign]. Clinvar id is 667737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NT5C2	NM_001351169.2	c.688-87T>G		intron_variant		ENST00000404739.8	NP_001338098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NT5C2	ENST00000404739.8	c.688-87T>G		intron_variant		1	NM_001351169.2	ENSP00000383960.3

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22124 AN: 152118 Hom.: 1772 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.150

GnomAD4 exome AF: 0.157 AC: 152134 AN: 968756 Hom.: 12504 AF XY: 0.157 AC XY: 78757 AN XY: 500342

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.0916

Gnomad4 ASJ exome AF: 0.186

Gnomad4 EAS exome AF: 0.141

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.166

Gnomad4 NFE exome AF: 0.162

Gnomad4 OTH exome AF: 0.157

GnomAD4 genome AF: 0.145 AC: 22125 AN: 152234 Hom.: 1771 Cov.: 32 AF XY: 0.144 AC XY: 10696 AN XY: 74422

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.150

Alfa AF: 0.151 Hom.: 1846

Bravo AF: 0.138

Asia WGS AF: 0.148 AC: 515 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	13
DANN	Benign	0.59

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: rs10786737; hg19: chr10-104857218; COSMIC: COSV58417684; COSMIC: COSV58417684;