rs2274339

Variant names:

• chr10-103100296-T-A
• rs2274339
• NM_001351169.2:c.540-277A>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001351169.2(NT5C2):​c.540-277A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,094 control chromosomes in the GnomAD database, including 7,506 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.31 (7506 hom., cov: 32)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.617
• Publications: 7 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):

• complex hereditary spastic paraplegia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-103100296-T-A is Benign according to our data. Variant chr10-103100296-T-A is described in ClinVar as Benign. ClinVar VariationId is 667538.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351169.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C2	NM_001351169.2	MANE Select	c.540-277A>T		intron	N/A	NP_001338098.1	P49902-1
	NT5C2	NM_001351170.2		c.564-277A>T		intron	N/A	NP_001338099.1	A0A6Q8PHP0
	NT5C2	NM_001351171.2		c.564-277A>T		intron	N/A	NP_001338100.1	A0A6Q8PHP0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NT5C2	ENST00000404739.8	TSL:1 MANE Select	c.540-277A>T		intron	N/A	ENSP00000383960.3	P49902-1
	NT5C2	ENST00000343289.9	TSL:1	c.540-277A>T		intron	N/A	ENSP00000339479.5	P49902-1
	NT5C2	ENST00000874311.1		c.756-277A>T		intron	N/A	ENSP00000544370.1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47329 AN: 151976 Hom.: 7500 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.245

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.314

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.311 AC: 47360 AN: 152094 Hom.: 7506 Cov.: 32 AF XY: 0.307 AC XY: 22831 AN XY: 74348

African (AFR) AF: 0.328 AC: 13609 AN: 41478

American (AMR) AF: 0.264 AC: 4034 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1253 AN: 3472

East Asian (EAS) AF: 0.208 AC: 1080 AN: 5188

South Asian (SAS) AF: 0.245 AC: 1179 AN: 4822

European-Finnish (FIN) AF: 0.289 AC: 3057 AN: 10562

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22076 AN: 67966

Other (OTH) AF: 0.313 AC: 662 AN: 2114

Alfa AF: 0.330 Hom.: 1039

Bravo AF: 0.310

Asia WGS AF: 0.226 AC: 785 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.14
DANN	Benign	0.51
PhyloP100		-0.62
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2274339;

hg19: chr10-104860053;