2-172504202-GA-G
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_001394928.1(ITGA6):c.3351delA(p.Lys1117AsnfsTer48) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000316 in 1,580,262 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Consequence
ITGA6
NM_001394928.1 frameshift
NM_001394928.1 frameshift
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 8.72
Publications
6 publications found
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]
ITGA6-AS1 (HGNC:40308): (ITGA6 antisense RNA 1)
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 4 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0124 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| ITGA6 | ENST00000442250.6 | c.3351delA | p.Lys1117AsnfsTer48 | frameshift_variant | Exon 26 of 26 | 5 | NM_001394928.1 | ENSP00000406694.1 | ||
| ITGA6 | ENST00000684293.1 | c.*142delA | 3_prime_UTR_variant | Exon 26 of 26 | NM_000210.4 | ENSP00000508249.1 |
Frequencies
GnomAD3 genomes 0.00000665 AC: 1AN: 150374Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
150374
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00000998 AC: 2AN: 200476 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
200476
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.00000280 AC: 4AN: 1429888Hom.: 0 Cov.: 31 AF XY: 0.00000423 AC XY: 3AN XY: 708650 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
4
AN:
1429888
Hom.:
Cov.:
31
AF XY:
AC XY:
3
AN XY:
708650
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
32612
American (AMR)
AF:
AC:
0
AN:
40148
Ashkenazi Jewish (ASJ)
AF:
AC:
1
AN:
25488
East Asian (EAS)
AF:
AC:
0
AN:
38520
South Asian (SAS)
AF:
AC:
0
AN:
81648
European-Finnish (FIN)
AF:
AC:
0
AN:
51598
Middle Eastern (MID)
AF:
AC:
0
AN:
5708
European-Non Finnish (NFE)
AF:
AC:
3
AN:
1094920
Other (OTH)
AF:
AC:
0
AN:
59246
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0104607), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.350
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
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10
<30
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35-40
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Age
GnomAD4 genome 0.00000665 AC: 1AN: 150374Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1AN XY: 73340 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
150374
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
73340
show subpopulations
African (AFR)
AF:
AC:
0
AN:
40904
American (AMR)
AF:
AC:
0
AN:
15102
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3452
East Asian (EAS)
AF:
AC:
0
AN:
5112
South Asian (SAS)
AF:
AC:
0
AN:
4748
European-Finnish (FIN)
AF:
AC:
0
AN:
10194
Middle Eastern (MID)
AF:
AC:
0
AN:
312
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67568
Other (OTH)
AF:
AC:
1
AN:
2076
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
0
2
4
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8
10
<30
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Age
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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