rs2274341

Positions:

• chr10-103093746-A-T

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.988+226T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 440,400 control chromosomes in the GnomAD database, including 7,930 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2562 hom., cov: 31)
  • Exomes 𝑓: 0.21 (5368 hom.)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.24

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=-0.9).
• BP6: Variant 10-103093746-A-T is Benign according to our data. Variant chr10-103093746-A-T is described in ClinVar as [Benign]. Clinvar id is 1255225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NT5C2	NM_001351169.2	c.988+226T>A		intron_variant		ENST00000404739.8	NP_001338098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NT5C2	ENST00000404739.8	c.988+226T>A		intron_variant		1	NM_001351169.2	ENSP00000383960	P1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 25880 AN: 150360 Hom.: 2561 Cov.: 31

Gnomad AFR AF: 0.0849

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.0863

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.150

GnomAD4 exome AF: 0.210 AC: 61009 AN: 289924 Hom.: 5368 Cov.: 3 AF XY: 0.207 AC XY: 31150 AN XY: 150184

Gnomad4 AFR exome AF: 0.0879

Gnomad4 AMR exome AF: 0.187

Gnomad4 ASJ exome AF: 0.224

Gnomad4 EAS exome AF: 0.106

Gnomad4 SAS exome AF: 0.130

Gnomad4 FIN exome AF: 0.244

Gnomad4 NFE exome AF: 0.237

Gnomad4 OTH exome AF: 0.202

GnomAD4 genome AF: 0.172 AC: 25876 AN: 150476 Hom.: 2562 Cov.: 31 AF XY: 0.171 AC XY: 12590 AN XY: 73464

Gnomad4 AFR AF: 0.0847

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.0863

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.149

Alfa AF: 0.194 Hom.: 427

Bravo AF: 0.161

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 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.061
DANN	Benign	0.23

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: rs2274341; hg19: chr10-104853503;