chr2-27232672-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate
The NM_004341.5(CAD):c.2870G>T(p.Gly957Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000805 in 1,614,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. G957G) has been classified as Likely benign.
Frequency
Consequence
NM_004341.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAD | NM_004341.5 | c.2870G>T | p.Gly957Val | missense_variant | 18/44 | ENST00000264705.9 | |
CAD | NM_001306079.2 | c.2681G>T | p.Gly894Val | missense_variant | 17/43 | ||
CAD | XM_047445803.1 | c.2870G>T | p.Gly957Val | missense_variant | 18/45 | ||
CAD | XM_006712101.4 | c.2681G>T | p.Gly894Val | missense_variant | 17/44 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAD | ENST00000264705.9 | c.2870G>T | p.Gly957Val | missense_variant | 18/44 | 1 | NM_004341.5 | P1 | |
CAD | ENST00000403525.5 | c.2681G>T | p.Gly894Val | missense_variant | 17/43 | 1 | |||
CAD | ENST00000464159.1 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152210Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461882Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727242
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74362
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, no assertion criteria provided | research | Gharavi Laboratory, Columbia University | Sep 16, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 19, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 957 of the CAD protein (p.Gly957Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CAD-related conditions. ClinVar contains an entry for this variant (Variation ID: 591744). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CAD protein function. 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. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 07, 2022 | The c.2870G>T (p.G957V) alteration is located in exon 18 (coding exon 18) of the CAD gene. This alteration results from a G to T substitution at nucleotide position 2870, causing the glycine (G) at amino acid position 957 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at