rs2293649
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001394928.1(ITGA6):c.2199C>T(p.Asp733=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,612,818 control chromosomes in the GnomAD database, including 54,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.25 ( 5321 hom., cov: 33)
Exomes 𝑓: 0.24 ( 49153 hom. )
Consequence
ITGA6
NM_001394928.1 synonymous
NM_001394928.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.04
Genes affected
ITGA6 (HGNC:6142): (integrin subunit alpha 6) The gene encodes a member of the integrin alpha chain family of proteins. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain that function in cell surface adhesion and signaling. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha 6 subunit. This subunit may associate with a beta 1 or beta 4 subunit to form an integrin that interacts with extracellular matrix proteins including members of the laminin family. The alpha 6 beta 4 integrin may promote tumorigenesis, while the alpha 6 beta 1 integrin may negatively regulate erbB2/HER2 signaling. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]
PDK1-AS1 (HGNC:40441): (PDK1 and ITGA6 antisense RNA 1)
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
Variant 2-172487375-C-T is Benign according to our data. Variant chr2-172487375-C-T is described in ClinVar as [Benign]. Clinvar id is 332369.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-172487375-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-2.04 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ITGA6 | NM_001394928.1 | c.2199C>T | p.Asp733= | synonymous_variant | 16/26 | ENST00000442250.6 | |
ITGA6 | NM_000210.4 | c.2082C>T | p.Asp694= | synonymous_variant | 15/26 | ENST00000684293.1 | |
LOC124900513 | XR_007087304.1 | n.704-6354G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ITGA6 | ENST00000442250.6 | c.2199C>T | p.Asp733= | synonymous_variant | 16/26 | 5 | NM_001394928.1 | ||
ITGA6 | ENST00000684293.1 | c.2082C>T | p.Asp694= | synonymous_variant | 15/26 | NM_000210.4 | P3 | ||
PDK1-AS1 | ENST00000442417.5 | n.769-6354G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.253 AC: 38456AN: 152008Hom.: 5314 Cov.: 33
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GnomAD3 exomes AF: 0.306 AC: 76760AN: 251228Hom.: 13582 AF XY: 0.303 AC XY: 41186AN XY: 135774
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GnomAD4 exome AF: 0.244 AC: 356353AN: 1460692Hom.: 49153 Cov.: 33 AF XY: 0.248 AC XY: 180531AN XY: 726742
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GnomAD4 genome ? AF: 0.253 AC: 38495AN: 152126Hom.: 5321 Cov.: 33 AF XY: 0.265 AC XY: 19687AN XY: 74348
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Junctional epidermolysis bullosa with pyloric atresia Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 19, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at