Genetic Variant NT5C2:c.1212-82T>C (chr10-103091078-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001351169.2(NT5C2):c.1212-82T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0998 in 1,256,530 control chromosomes in the GnomAD database, including 8,082 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.094 ( 880 hom., cov: 32)

Exomes 𝑓: 0.10 ( 7202 hom. )

Consequence

NT5C2
NM_001351169.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.403

Publications

21 publications found

Variant links:

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

NT5C2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 10-103091078-A-G is Benign according to our data. Variant chr10-103091078-A-G is described in ClinVar as [Benign]. Clinvar id is 1295697.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C2	NM_001351169.2 link	c.1212-82T>C		intron_variant	Intron 16 of 18	ENST00000404739.8	NP_001338098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C2	ENST00000404739.8 link	c.1212-82T>C		intron_variant	Intron 16 of 18	1	NM_001351169.2	ENSP00000383960.3		P49902-1

Frequencies

GnomAD3 genomes

AF:

0.0940

AC:

14302

AN:

152106

Hom.:

874

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0598

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.138

Gnomad ASJ

AF:

0.0700

Gnomad EAS

AF:

0.279

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.0745

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0898

Gnomad OTH

AF:

0.101

GnomAD4 exome

AF:

0.101

AC:

111048

AN:

1104304

Hom.:

7202

AF XY:

0.104

AC XY:

58508

AN XY:

564520

show subpopulations

African (AFR)

AF:

0.0535

AC:

1397

AN:

26100

American (AMR)

AF:

0.202

AC:

8544

AN:

42354

Ashkenazi Jewish (ASJ)

AF:

0.0754

AC:

1796

AN:

23810

East Asian (EAS)

AF:

0.262

AC:

9665

AN:

36942

South Asian (SAS)

AF:

0.196

AC:

15233

AN:

77644

European-Finnish (FIN)

AF:

0.0771

AC:

3015

AN:

39080

Middle Eastern (MID)

AF:

0.0913

AC:

468

AN:

5128

European-Non Finnish (NFE)

AF:

0.0821

AC:

66006

AN:

804300

Other (OTH)

AF:

0.101

AC:

4924

AN:

48946

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

4839

9678

14517

19356

24195

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0941

AC:

14322

AN:

152226

Hom.:

880

Cov.:

AF XY:

0.0960

AC XY:

7146

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0599

AC:

2491

AN:

41552

American (AMR)

AF:

0.138

AC:

2112

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0700

AC:

243

AN:

3470

East Asian (EAS)

AF:

0.279

AC:

1443

AN:

5168

South Asian (SAS)

AF:

0.182

AC:

879

AN:

4820

European-Finnish (FIN)

AF:

0.0745

AC:

790

AN:

10604

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0898

AC:

6108

AN:

68008

Other (OTH)

AF:

0.104

AC:

219

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

637

1274

1912

2549

3186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0896

Hom.:

Bravo

AF:

0.0979

Asia WGS

AF:

0.196

AC:

680

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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

-0.80

CADD

Benign

4.1

(source)

DANN

Benign

0.62

PhyloP100

0.40

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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10-103091078-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over