10-102918595-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 3P and 3B. PM2PP2BP4_ModerateBS1_Supporting
The NM_017649.5(CNNM2):c.115G>A(p.Gly39Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000172 in 1,565,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_017649.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CNNM2 | NM_017649.5 | c.115G>A | p.Gly39Arg | missense_variant | 1/8 | ENST00000369878.9 | |
CNNM2 | NM_199076.3 | c.115G>A | p.Gly39Arg | missense_variant | 1/7 | ||
CNNM2 | NM_199077.3 | c.115G>A | p.Gly39Arg | missense_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CNNM2 | ENST00000369878.9 | c.115G>A | p.Gly39Arg | missense_variant | 1/8 | 1 | NM_017649.5 | P4 | |
CNNM2 | ENST00000369875.3 | c.115G>A | p.Gly39Arg | missense_variant | 1/2 | 1 | |||
CNNM2 | ENST00000433628.2 | c.115G>A | p.Gly39Arg | missense_variant | 1/7 | 2 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152192Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000121 AC: 2AN: 165650Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 91520
GnomAD4 exome AF: 0.00000991 AC: 14AN: 1413282Hom.: 0 Cov.: 32 AF XY: 0.00000429 AC XY: 3AN XY: 699636
GnomAD4 genome AF: 0.0000854 AC: 13AN: 152306Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74478
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 11, 2021 | The c.115G>A (p.G39R) alteration is located in exon 1 (coding exon 1) of the CNNM2 gene. This alteration results from a G to A substitution at nucleotide position 115, causing the glycine (G) at amino acid position 39 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 25, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 39 of the CNNM2 protein (p.Gly39Arg). This variant is present in population databases (rs765571636, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with CNNM2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at