Variant 10-103089359-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017649.5(CNNM2):c.*12179G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 277,202 control chromosomes in the GnomAD database, including 2,299 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1063 hom., cov: 32)

Exomes 𝑓: 0.13 ( 1236 hom. )

Consequence

CNNM2
NM_017649.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.275

Variant links:

Genes affected

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 links:

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 10-103089359-G-C is Benign according to our data. Variant chr10-103089359-G-C is described in ClinVar as [Benign]. Clinvar id is 1168446.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
CNNM2	NM_017649.5 link	c.*12179G>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000369878.9	NP_060119.3	Q9H8M5-1
NT5C2	NM_001351169.2 link	c.*313C>G		3_prime_UTR_variant	Exon 19 of 19	ENST00000404739.8	NP_001338098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNNM2	ENST00000369878.9 link	c.*12179G>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_017649.5	ENSP00000358894.3		Q9H8M5-1
NT5C2	ENST00000404739 link	c.*313C>G		3_prime_UTR_variant	Exon 19 of 19	1	NM_001351169.2	ENSP00000383960.3		P49902-1

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15780

AN:

151994

Hom.:

1059

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0442

Gnomad AMI

AF:

0.0548

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.116

Gnomad EAS

AF:

0.279

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.0857

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.118

GnomAD4 exome

AF:

0.126

AC:

15731

AN:

125090

Hom.:

1236

Cov.:

AF XY:

0.125

AC XY:

7568

AN XY:

60512

show subpopulations

Gnomad4 AFR exome

AF:

0.0394

Gnomad4 AMR exome

AF:

0.184

Gnomad4 ASJ exome

AF:

0.118

Gnomad4 EAS exome

AF:

0.255

Gnomad4 SAS exome

AF:

0.195

Gnomad4 FIN exome

AF:

0.0834

Gnomad4 NFE exome

AF:

0.107

Gnomad4 OTH exome

AF:

0.123

GnomAD4 genome

AF:

0.104

AC:

15792

AN:

152112

Hom.:

1063

Cov.:

AF XY:

0.106

AC XY:

7859

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0443

Gnomad4 AMR

AF:

0.155

Gnomad4 ASJ

AF:

0.116

Gnomad4 EAS

AF:

0.279

Gnomad4 SAS

AF:

0.191

Gnomad4 FIN

AF:

0.0857

Gnomad4 NFE

AF:

0.112

Gnomad4 OTH

AF:

0.121

Alfa

AF:

0.102

Hom.:

118

Bravo

AF:

0.107

Asia WGS

AF:

0.204

AC:

708

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	This variant is associated with the following publications: (PMID: 25814643) -

Hereditary spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Nov 18, 2020

- -

Hereditary spastic paraplegia 45

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 06, 2025

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.0

DANN

Benign

0.55

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over