rs537950420
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BS1_SupportingBS2
The NM_002206.3(ITGA7):āc.671G>Cā(p.Gly224Ala) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000539 in 1,613,946 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_002206.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITGA7 | NM_002206.3 | c.671G>C | p.Gly224Ala | missense_variant, splice_region_variant | 5/25 | ENST00000257879.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITGA7 | ENST00000257879.11 | c.671G>C | p.Gly224Ala | missense_variant, splice_region_variant | 5/25 | 1 | NM_002206.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000336 AC: 51AN: 151978Hom.: 3 Cov.: 32
GnomAD3 exomes AF: 0.0000478 AC: 12AN: 251032Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135742
GnomAD4 exome AF: 0.0000239 AC: 35AN: 1461850Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 10AN XY: 727220
GnomAD4 genome ? AF: 0.000342 AC: 52AN: 152096Hom.: 3 Cov.: 32 AF XY: 0.000417 AC XY: 31AN XY: 74334
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 19, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 224 of the ITGA7 protein (p.Gly224Ala). This variant is present in population databases (rs537950420, gnomAD 0.01%). 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: 537988). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 | Nov 09, 2023 | - - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jun 09, 2023 | PP3 - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jan 21, 2022 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 12, 2024 | The c.671G>C (p.G224A) alteration is located in exon 5 (coding exon 5) of the ITGA7 gene. This alteration results from a G to C substitution at nucleotide position 671, causing the glycine (G) at amino acid position 224 to be replaced by an alanine (A). 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