rs786205910
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP2PP3_StrongPP5
The NM_017649.5(CNNM2):c.1069G>A(p.Glu357Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
CNNM2
NM_017649.5 missense
NM_017649.5 missense
Scores
14
4
1
Clinical Significance
Conservation
PhyloP100: 9.94
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PM1
?
In a domain CNNM transmembrane (size 180) in uniprot entity CNNM2_HUMAN there are 11 pathogenic changes around while only 2 benign (85%) in NM_017649.5
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, CNNM2
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.965
PP5
?
Variant 10-102919549-G-A is Pathogenic according to our data. Variant chr10-102919549-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 192324.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNNM2 | NM_017649.5 | c.1069G>A | p.Glu357Lys | missense_variant | 1/8 | ENST00000369878.9 | |
CNNM2 | NM_199076.3 | c.1069G>A | p.Glu357Lys | missense_variant | 1/7 | ||
CNNM2 | NM_199077.3 | c.1069G>A | p.Glu357Lys | missense_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNNM2 | ENST00000369878.9 | c.1069G>A | p.Glu357Lys | missense_variant | 1/8 | 1 | NM_017649.5 | P4 | |
CNNM2 | ENST00000369875.3 | c.1069G>A | p.Glu357Lys | missense_variant | 1/2 | 1 | |||
CNNM2 | ENST00000433628.2 | c.1069G>A | p.Glu357Lys | missense_variant | 1/7 | 2 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Hypomagnesemia, seizures, and intellectual disability 1 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 01, 2014 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;H;H
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;.;D
Vest4
MutPred
Loss of sheet (P = 0.0037);Loss of sheet (P = 0.0037);Loss of sheet (P = 0.0037);
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
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