dbSNP rs774541114: NT5C2:p.Glu559Glu (chr10-103089681-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS1

The NM_001351169.2(NT5C2):c.1677G>A(p.Glu559Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 1,514,580 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000066 ( 0 hom. )

Consequence

NT5C2
NM_001351169.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.477

Publications

0 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, AD, SD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Illumina, ClinGen
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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 10-103089681-C-T is Benign according to our data. Variant chr10-103089681-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3631686.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.477 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0000724 (11/151846) while in subpopulation AFR AF = 0.000242 (10/41316). AF 95% confidence interval is 0.000131. There are 0 homozygotes in GnomAd4. There are 5 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NT5C2	NM_001351169.2	MANE Select	c.1677G>A	p.Glu559Glu	synonymous	Exon 19 of 19	NP_001338098.1	P49902-1
CNNM2	NM_017649.5	MANE Select	c.*12501C>T		3_prime_UTR	Exon 8 of 8	NP_060119.3
NT5C2	NM_001351170.2		c.1701G>A	p.Glu567Glu	synonymous	Exon 19 of 19	NP_001338099.1	A0A6Q8PHP0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NT5C2	ENST00000404739.8	TSL:1 MANE Select	c.1677G>A	p.Glu559Glu	synonymous	Exon 19 of 19	ENSP00000383960.3	P49902-1
NT5C2	ENST00000343289.9	TSL:1	c.1677G>A	p.Glu559Glu	synonymous	Exon 18 of 18	ENSP00000339479.5	P49902-1
CNNM2	ENST00000369878.9	TSL:1 MANE Select	c.*12501C>T		3_prime_UTR	Exon 8 of 8	ENSP00000358894.3	Q9H8M5-1

Frequencies

GnomAD3 genomes

AF:

0.0000724

AC:

AN:

151846

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000361

AC:

AN:

221496

AF XY:

0.0000252

show subpopulations

Gnomad AFR exome

AF:

0.000132

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000993

Gnomad NFE exome

AF:

0.0000295

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000660

AC:

AN:

1362734

Hom.:

Cov.:

AF XY:

0.00000740

AC XY:

AN XY:

675826

show subpopulations

African (AFR)

AF:

0.0000648

AC:

AN:

30860

American (AMR)

AF:

0.00

AC:

AN:

38954

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23162

East Asian (EAS)

AF:

0.00

AC:

AN:

37524

South Asian (SAS)

AF:

0.0000265

AC:

AN:

75408

European-Finnish (FIN)

AF:

0.0000198

AC:

AN:

50524

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5210

European-Non Finnish (NFE)

AF:

0.00000287

AC:

AN:

1044968

Other (OTH)

AF:

0.0000178

AC:

AN:

56124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000724

AC:

AN:

151846

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

74182

show subpopulations

African (AFR)

AF:

0.000242

AC:

AN:

41316

American (AMR)

AF:

0.0000656

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10562

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67946

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000986

Hom.:

Bravo

AF:

0.0000529

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hereditary spastic paraplegia 45 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.84

(source)

DANN

Benign

0.42

PhyloP100

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over