10-103089711-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001351169.2(NT5C2):c.1647C>T(p.Asp549Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 1,611,386 control chromosomes in the GnomAD database, including 129,685 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 12616 hom., cov: 30)

Exomes 𝑓: 0.40 ( 117069 hom. )

Consequence

NT5C2
NM_001351169.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.259

Publications

43 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 links:

CNNM2 (HGNC:103): (cyclin and CBS domain divalent metal cation transport mediator 2) This gene encodes a member of the ancient conserved domain containing protein family. Members of this protein family contain a cyclin box motif and have structural similarity to the cyclins. The encoded protein may play an important role in magnesium homeostasis by mediating the epithelial transport and renal reabsorption of Mg2+. Mutations in this gene are associated with renal hypomagnesemia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

CNNM2 Gene-Disease associations (from GenCC):

hypomagnesemia, seizures, and intellectual disability 1
Inheritance: AR, SD, AD Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Illumina, Labcorp Genetics (formerly Invitae)
renal hypomagnesemia 6
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
familial primary hypomagnesemia with normocalciuria and normocalcemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CNNM2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 10-103089711-G-A is Benign according to our data. Variant chr10-103089711-G-A is described in ClinVar as [Benign]. Clinvar id is 380852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.259 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NT5C2	NM_001351169.2 link	c.1647C>T	p.Asp549Asp	synonymous_variant	Exon 19 of 19	ENST00000404739.8	NP_001338098.1
CNNM2	NM_017649.5 link	c.*12531G>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000369878.9	NP_060119.3	Q9H8M5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NT5C2	ENST00000404739.8 link	c.1647C>T	p.Asp549Asp	synonymous_variant	Exon 19 of 19	1	NM_001351169.2	ENSP00000383960.3		P49902-1
CNNM2	ENST00000369878.9 link	c.*12531G>A		3_prime_UTR_variant	Exon 8 of 8	1	NM_017649.5	ENSP00000358894.3		Q9H8M5-1

Frequencies

GnomAD3 genomes

AF:

0.405

AC:

61405

AN:

151448

Hom.:

12605

Cov.:

show subpopulations

Gnomad AFR

AF:

0.388

Gnomad AMI

AF:

0.351

Gnomad AMR

AF:

0.403

Gnomad ASJ

AF:

0.431

Gnomad EAS

AF:

0.475

Gnomad SAS

AF:

0.427

Gnomad FIN

AF:

0.365

Gnomad MID

AF:

0.427

Gnomad NFE

AF:

0.415

Gnomad OTH

AF:

0.416

GnomAD2 exomes

AF:

0.413

AC:

103054

AN:

249798

AF XY:

0.414

show subpopulations

Gnomad AFR exome

AF:

0.385

Gnomad AMR exome

AF:

0.414

Gnomad ASJ exome

AF:

0.424

Gnomad EAS exome

AF:

0.475

Gnomad FIN exome

AF:

0.367

Gnomad NFE exome

AF:

0.408

Gnomad OTH exome

AF:

0.412

GnomAD4 exome

AF:

0.399

AC:

582541

AN:

1459820

Hom.:

117069

Cov.:

AF XY:

0.400

AC XY:

290702

AN XY:

726162

show subpopulations

African (AFR)

AF:

0.385

AC:

12875

AN:

33412

American (AMR)

AF:

0.419

AC:

18638

AN:

44500

Ashkenazi Jewish (ASJ)

AF:

0.421

AC:

10955

AN:

26018

East Asian (EAS)

AF:

0.413

AC:

16380

AN:

39666

South Asian (SAS)

AF:

0.438

AC:

37632

AN:

85944

European-Finnish (FIN)

AF:

0.366

AC:

19516

AN:

53364

Middle Eastern (MID)

AF:

0.438

AC:

2481

AN:

5668

European-Non Finnish (NFE)

AF:

0.396

AC:

439524

AN:

1110952

Other (OTH)

AF:

0.407

AC:

24540

AN:

60296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

17497

34994

52491

69988

87485

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.405

AC:

61457

AN:

151566

Hom.:

12616

Cov.:

AF XY:

0.403

AC XY:

29827

AN XY:

74032

show subpopulations

African (AFR)

AF:

0.388

AC:

15991

AN:

41202

American (AMR)

AF:

0.403

AC:

6141

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.431

AC:

1494

AN:

3464

East Asian (EAS)

AF:

0.474

AC:

2445

AN:

5154

South Asian (SAS)

AF:

0.426

AC:

2041

AN:

4788

European-Finnish (FIN)

AF:

0.365

AC:

3833

AN:

10500

Middle Eastern (MID)

AF:

0.435

AC:

128

AN:

294

European-Non Finnish (NFE)

AF:

0.415

AC:

28184

AN:

67902

Other (OTH)

AF:

0.419

AC:

881

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1805

3610

5414

7219

9024

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.410

Hom.:

22075

Bravo

AF:

0.407

Asia WGS

AF:

0.415

AC:

1441

AN:

3478

EpiCase

AF:

0.405

EpiControl

AF:

0.408

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Jan 22, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Hereditary spastic paraplegia 45

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.47

CADD

Benign

(source)

DANN

Benign

0.41

PhyloP100

0.26

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

10-103089711-G-A

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