rs1926029

Variant names:

• chr10-103095913-G-A
• rs1926029
• NM_001351169.2:c.813+26C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001351169.2(NT5C2):​c.813+26C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,577,372 control chromosomes in the GnomAD database, including 73,626 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7538 hom., cov: 31)
  • Exomes 𝑓: 0.30 (66088 hom.)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.583
• Publications: 19 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 10-103095913-G-A is Benign according to our data. Variant chr10-103095913-G-A is described in ClinVar as Benign. ClinVar VariationId is 667734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 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.813+26C>T		intron	N/A	NP_001338098.1	P49902-1
	NT5C2	NM_001351170.2		c.837+26C>T		intron	N/A	NP_001338099.1	A0A6Q8PHP0
	NT5C2	NM_001351171.2		c.837+26C>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.813+26C>T		intron	N/A	ENSP00000383960.3	P49902-1
	NT5C2	ENST00000343289.9	TSL:1	c.813+26C>T		intron	N/A	ENSP00000339479.5	P49902-1
	NT5C2	ENST00000874311.1		c.1029+26C>T		intron	N/A	ENSP00000544370.1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47405 AN: 151818 Hom.: 7533 Cov.: 31

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.315

GnomAD2 exomes AF: 0.286 AC: 71564 AN: 249880 AF XY: 0.288

Gnomad AFR exome AF: 0.327

Gnomad AMR exome AF: 0.207

Gnomad ASJ exome AF: 0.352

Gnomad EAS exome AF: 0.214

Gnomad FIN exome AF: 0.289

Gnomad NFE exome AF: 0.321

Gnomad OTH exome AF: 0.305

GnomAD4 exome AF: 0.300 AC: 427314 AN: 1425436 Hom.: 66088 Cov.: 26 AF XY: 0.299 AC XY: 212607 AN XY: 711314

African (AFR) AF: 0.331 AC: 10806 AN: 32684

American (AMR) AF: 0.215 AC: 9543 AN: 44402

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 9001 AN: 25874

East Asian (EAS) AF: 0.160 AC: 6320 AN: 39502

South Asian (SAS) AF: 0.240 AC: 20444 AN: 85320

European-Finnish (FIN) AF: 0.289 AC: 15419 AN: 53372

Middle Eastern (MID) AF: 0.347 AC: 1971 AN: 5688

European-Non Finnish (NFE) AF: 0.311 AC: 335780 AN: 1079406

Other (OTH) AF: 0.305 AC: 18030 AN: 59188

GnomAD4 genome AF: 0.312 AC: 47435 AN: 151936 Hom.: 7538 Cov.: 31 AF XY: 0.308 AC XY: 22863 AN XY: 74254

African (AFR) AF: 0.329 AC: 13609 AN: 41416

American (AMR) AF: 0.264 AC: 4041 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1266 AN: 3464

East Asian (EAS) AF: 0.208 AC: 1077 AN: 5176

South Asian (SAS) AF: 0.244 AC: 1175 AN: 4812

European-Finnish (FIN) AF: 0.291 AC: 3064 AN: 10532

Middle Eastern (MID) AF: 0.363 AC: 106 AN: 292

European-Non Finnish (NFE) AF: 0.326 AC: 22129 AN: 67934

Other (OTH) AF: 0.315 AC: 665 AN: 2114

Alfa AF: 0.324 Hom.: 2200

Bravo AF: 0.310

Asia WGS AF: 0.224 AC: 779 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
DANN	Benign	0.63
PhyloP100		0.58
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: rs1926029; hg19: chr10-104855670; COSMIC: COSV58417337; COSMIC: COSV58417337;