NM_017649.5:c.117delG
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_017649.5(CNNM2):c.117delG(p.Ile40SerfsTer15) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CNNM2
NM_017649.5 frameshift
NM_017649.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.46
Publications
3 publications found
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 Gene-Disease associations (from GenCC):
- hypomagnesemia, seizures, and intellectual disability 1Inheritance: SD, AD, AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Illumina, Labcorp Genetics (formerly Invitae), G2P
- renal hypomagnesemia 6Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- familial primary hypomagnesemia with normocalciuria and normocalcemiaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 10-102918592-CG-C is Pathogenic according to our data. Variant chr10-102918592-CG-C is described in ClinVar as Pathogenic. ClinVar VariationId is 30683.Status of the report is no_assertion_criteria_provided, 0 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_017649.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CNNM2 | NM_017649.5 | MANE Select | c.117delG | p.Ile40SerfsTer15 | frameshift | Exon 1 of 8 | NP_060119.3 | ||
| CNNM2 | NM_199076.3 | c.117delG | p.Ile40SerfsTer15 | frameshift | Exon 1 of 7 | NP_951058.1 | Q9H8M5-2 | ||
| CNNM2 | NM_199077.3 | c.117delG | p.Ile40SerfsTer15 | frameshift | Exon 1 of 2 | NP_951059.1 | Q9H8M5-3 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CNNM2 | ENST00000369878.9 | TSL:1 MANE Select | c.117delG | p.Ile40SerfsTer15 | frameshift | Exon 1 of 8 | ENSP00000358894.3 | Q9H8M5-1 | |
| CNNM2 | ENST00000369875.3 | TSL:1 | c.117delG | p.Ile40SerfsTer15 | frameshift | Exon 1 of 2 | ENSP00000358891.3 | Q9H8M5-3 | |
| CNNM2 | ENST00000970832.1 | c.117delG | p.Ile40SerfsTer15 | frameshift | Exon 1 of 7 | ENSP00000640891.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1414874Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 700638
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1414874
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
700638
African (AFR)
AF:
AC:
0
AN:
30566
American (AMR)
AF:
AC:
0
AN:
37784
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24912
East Asian (EAS)
AF:
AC:
0
AN:
36512
South Asian (SAS)
AF:
AC:
0
AN:
81056
European-Finnish (FIN)
AF:
AC:
0
AN:
48222
Middle Eastern (MID)
AF:
AC:
0
AN:
5152
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1092086
Other (OTH)
AF:
AC:
0
AN:
58584
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic
Revision:no assertion criteria provided
Pathogenic
VUS
Benign
Condition
1
-
-
Renal hypomagnesemia 6 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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