rs17854598
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_002206.3(ITGA7):c.1625G>A(p.Arg542His) variant causes a missense change. The variant allele was found at a frequency of 0.000105 in 1,613,948 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. R542C) 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.1625G>A | p.Arg542His | missense_variant | 12/25 | ENST00000257879.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITGA7 | ENST00000257879.11 | c.1625G>A | p.Arg542His | missense_variant | 12/25 | 1 | NM_002206.3 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251260Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135808
GnomAD4 exome AF: 0.000108 AC: 158AN: 1461768Hom.: 0 Cov.: 33 AF XY: 0.000105 AC XY: 76AN XY: 727170
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74322
ClinVar
Submissions by phenotype
Congenital muscular dystrophy due to integrin alpha-7 deficiency Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 01, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 26, 2022 | 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. 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"). ClinVar contains an entry for this variant (Variation ID: 449648). This variant has not been reported in the literature in individuals affected with ITGA7-related conditions. This variant is present in population databases (rs17854598, gnomAD 0.008%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 542 of the ITGA7 protein (p.Arg542His). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 30, 2017 | A variant of uncertain significance has been identified in the ITGA7 gene. The R542H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R542H variant is observed in 2/24012 (0.01%) alleles from individuals of African background (Lek et al., 2016). The R542H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species; and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at