rs2066323

Variant names:

• chr10-103111604-A-G
• rs2066323
• NM_001351169.2:c.176-4898T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001351169.2(NT5C2):​c.176-4898T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 489,176 control chromosomes in the GnomAD database, including 41,923 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.41 (12973 hom., cov: 31)
  • Exomes 𝑓: 0.41 (28950 hom.)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71
• Publications: 13 publications found

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]

NT5C2 Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia 45

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C2	NM_001351169.2	c.176-4898T>C		intron_variant	Intron 4 of 18	ENST00000404739.8	NP_001338098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C2	ENST00000404739.8	c.176-4898T>C		intron_variant	Intron 4 of 18	1	NM_001351169.2	ENSP00000383960.3

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62224 AN: 151818 Hom.: 12955 Cov.: 31

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.420

GnomAD4 exome AF: 0.411 AC: 138557 AN: 337240 Hom.: 28950 AF XY: 0.410 AC XY: 69121 AN XY: 168496

African (AFR) AF: 0.393 AC: 3424 AN: 8716

American (AMR) AF: 0.428 AC: 3207 AN: 7500

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 4166 AN: 9744

East Asian (EAS) AF: 0.467 AC: 10818 AN: 23186

South Asian (SAS) AF: 0.454 AC: 1806 AN: 3982

European-Finnish (FIN) AF: 0.370 AC: 7653 AN: 20704

Middle Eastern (MID) AF: 0.441 AC: 654 AN: 1482

European-Non Finnish (NFE) AF: 0.407 AC: 98766 AN: 242758

Other (OTH) AF: 0.421 AC: 8063 AN: 19168

GnomAD4 genome AF: 0.410 AC: 62287 AN: 151936 Hom.: 12973 Cov.: 31 AF XY: 0.408 AC XY: 30324 AN XY: 74250

African (AFR) AF: 0.390 AC: 16149 AN: 41456

American (AMR) AF: 0.403 AC: 6148 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1512 AN: 3470

East Asian (EAS) AF: 0.558 AC: 2877 AN: 5152

South Asian (SAS) AF: 0.448 AC: 2152 AN: 4806

European-Finnish (FIN) AF: 0.367 AC: 3873 AN: 10550

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28235 AN: 67932

Other (OTH) AF: 0.423 AC: 892 AN: 2108

Alfa AF: 0.407 Hom.: 4821

Bravo AF: 0.412

Asia WGS AF: 0.469 AC: 1626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	17
DANN	Benign	0.54
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2066323; hg19: chr10-104871361;