rs2274341

Variant names:

• chr10-103093746-A-T
• rs2274341
• NM_001351169.2:c.988+226T>A

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.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
• Publications: 6 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=-0.9).
• BP6: Variant 10-103093746-A-T is Benign according to our data. Variant chr10-103093746-A-T is described in ClinVar as Benign. ClinVar VariationId 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.

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.988+226T>A		intron	N/A	NP_001338098.1	P49902-1
	NT5C2	NM_001351170.2		c.1012+226T>A		intron	N/A	NP_001338099.1	A0A6Q8PHP0
	NT5C2	NM_001351171.2		c.1012+226T>A		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.988+226T>A		intron	N/A	ENSP00000383960.3	P49902-1
	NT5C2	ENST00000343289.9	TSL:1	c.988+226T>A		intron	N/A	ENSP00000339479.5	P49902-1
	NT5C2	ENST00000874311.1		c.1204+226T>A		intron	N/A	ENSP00000544370.1

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

African (AFR) AF: 0.0879 AC: 784 AN: 8920

American (AMR) AF: 0.187 AC: 2259 AN: 12096

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 2147 AN: 9580

East Asian (EAS) AF: 0.106 AC: 2383 AN: 22446

South Asian (SAS) AF: 0.130 AC: 2601 AN: 19944

European-Finnish (FIN) AF: 0.244 AC: 4660 AN: 19104

Middle Eastern (MID) AF: 0.137 AC: 177 AN: 1290

European-Non Finnish (NFE) AF: 0.237 AC: 42470 AN: 179104

Other (OTH) AF: 0.202 AC: 3528 AN: 17440

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

African (AFR) AF: 0.0847 AC: 3463 AN: 40868

American (AMR) AF: 0.178 AC: 2687 AN: 15082

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 710 AN: 3458

East Asian (EAS) AF: 0.0863 AC: 442 AN: 5120

South Asian (SAS) AF: 0.111 AC: 527 AN: 4766

European-Finnish (FIN) AF: 0.227 AC: 2344 AN: 10346

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.226 AC: 15256 AN: 67572

Other (OTH) AF: 0.149 AC: 307 AN: 2064

Alfa AF: 0.194 Hom.: 427

Bravo AF: 0.161

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	-0.90
CADD	Benign	0.061
DANN	Benign	0.23
PhyloP100		-1.2
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: rs2274341; hg19: chr10-104853503;