10-103095899-T-C

Variant names:

• chr10-103095899-T-C
• rs1926030
• NM_001351169.2:c.813+40A>G

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+40A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 1,532,738 control chromosomes in the GnomAD database, including 123,736 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (13016 hom., cov: 31)
  • Exomes 𝑓: 0.40 (110720 hom.)
• Consequence: NT5C2 NM_001351169.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.104
• Publications: 22 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-103095899-T-C is Benign according to our data. Variant chr10-103095899-T-C is described in ClinVar as Benign. ClinVar VariationId is 1235346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C2	NM_001351169.2	c.813+40A>G		intron_variant	Intron 12 of 18	ENST00000404739.8	NP_001338098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C2	ENST00000404739.8	c.813+40A>G		intron_variant	Intron 12 of 18	1	NM_001351169.2	ENSP00000383960.3

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62358 AN: 151846 Hom.: 13003 Cov.: 31

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.421

GnomAD2 exomes AF: 0.423 AC: 105460 AN: 249090 AF XY: 0.425

Gnomad AFR exome AF: 0.386

Gnomad AMR exome AF: 0.415

Gnomad ASJ exome AF: 0.433

Gnomad EAS exome AF: 0.564

Gnomad FIN exome AF: 0.374

Gnomad NFE exome AF: 0.409

Gnomad OTH exome AF: 0.420

GnomAD4 exome AF: 0.397 AC: 548607 AN: 1380772 Hom.: 110720 Cov.: 22 AF XY: 0.400 AC XY: 276585 AN XY: 691476

African (AFR) AF: 0.380 AC: 12070 AN: 31738

American (AMR) AF: 0.419 AC: 18543 AN: 44214

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 10941 AN: 25596

East Asian (EAS) AF: 0.501 AC: 19685 AN: 39282

South Asian (SAS) AF: 0.455 AC: 38280 AN: 84182

European-Finnish (FIN) AF: 0.373 AC: 19912 AN: 53322

Middle Eastern (MID) AF: 0.437 AC: 2455 AN: 5624

European-Non Finnish (NFE) AF: 0.388 AC: 403183 AN: 1039148

Other (OTH) AF: 0.408 AC: 23538 AN: 57666

GnomAD4 genome AF: 0.411 AC: 62414 AN: 151966 Hom.: 13016 Cov.: 31 AF XY: 0.409 AC XY: 30381 AN XY: 74264

African (AFR) AF: 0.389 AC: 16127 AN: 41444

American (AMR) AF: 0.404 AC: 6176 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1527 AN: 3468

East Asian (EAS) AF: 0.557 AC: 2884 AN: 5176

South Asian (SAS) AF: 0.450 AC: 2164 AN: 4814

European-Finnish (FIN) AF: 0.368 AC: 3882 AN: 10548

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.417 AC: 28310 AN: 67914

Other (OTH) AF: 0.424 AC: 896 AN: 2112

Alfa AF: 0.416 Hom.: 16448

Bravo AF: 0.412

Asia WGS AF: 0.465 AC: 1614 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.43
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1926030; hg19: chr10-104855656; COSMIC: COSV58415391; COSMIC: COSV58415391;