chr2-172427843-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_001394928.1(ITGA6):c.55C>T(p.Arg19Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000772 in 1,605,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001394928.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITGA6 | NM_001394928.1 | c.55C>T | p.Arg19Trp | missense_variant | 1/26 | ENST00000442250.6 | |
ITGA6 | NM_000210.4 | c.55C>T | p.Arg19Trp | missense_variant | 1/26 | ENST00000684293.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITGA6 | ENST00000442250.6 | c.55C>T | p.Arg19Trp | missense_variant | 1/26 | 5 | NM_001394928.1 | ||
ITGA6 | ENST00000684293.1 | c.55C>T | p.Arg19Trp | missense_variant | 1/26 | NM_000210.4 | P3 | ||
ENST00000441212.1 | n.489G>A | non_coding_transcript_exon_variant | 2/2 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000177 AC: 27AN: 152122Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000132 AC: 31AN: 235652Hom.: 0 AF XY: 0.000124 AC XY: 16AN XY: 129320
GnomAD4 exome AF: 0.0000667 AC: 97AN: 1453310Hom.: 0 Cov.: 34 AF XY: 0.0000747 AC XY: 54AN XY: 722954
GnomAD4 genome ? AF: 0.000177 AC: 27AN: 152230Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74418
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 22, 2022 | The c.55C>T (p.R19W) alteration is located in exon 1 (coding exon 1) of the ITGA6 gene. This alteration results from a C to T substitution at nucleotide position 55, causing the arginine (R) at amino acid position 19 to be replaced by a tryptophan (W). 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 | Invitae | Aug 19, 2022 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 19 of the ITGA6 protein (p.Arg19Trp). This variant is present in population databases (rs150472149, gnomAD 0.09%). This variant has not been reported in the literature in individuals affected with ITGA6-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The tryptophan amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at