12-55703126-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_002206.3(ITGA7):c.259C>T(p.Arg87Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000552 in 1,613,424 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R87H) has been classified as Uncertain significance.
Frequency
Consequence
NM_002206.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITGA7 | NM_002206.3 | c.259C>T | p.Arg87Cys | missense_variant | 2/25 | ENST00000257879.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITGA7 | ENST00000257879.11 | c.259C>T | p.Arg87Cys | missense_variant | 2/25 | 1 | NM_002206.3 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152166Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000400 AC: 10AN: 250224Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135356
GnomAD4 exome AF: 0.0000561 AC: 82AN: 1461258Hom.: 0 Cov.: 36 AF XY: 0.0000605 AC XY: 44AN XY: 726956
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152166Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74324
ClinVar
Submissions by phenotype
Congenital muscular dystrophy due to integrin alpha-7 deficiency Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 12, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 87 of the ITGA7 protein (p.Arg87Cys). This variant is present in population databases (rs140570573, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with ITGA7-related conditions. ClinVar contains an entry for this variant (Variation ID: 470575). 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: "Probably Damaging"; 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Sep 19, 2019 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 18, 2023 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at