chr2-172427667-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000210.4(ITGA6):​c.-122C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000098 in 1,326,360 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000090 ( 1 hom. )

Consequence

ITGA6
NM_000210.4 5_prime_UTR_premature_start_codon_gain

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.583
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.32).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ITGA6NM_001394928.1 linkc.-122C>T 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 26 ENST00000442250.6 NP_001381857.1
ITGA6NM_000210.4 linkc.-122C>T 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 26 ENST00000684293.1 NP_000201.2 P23229-2
ITGA6NM_001394928.1 linkc.-122C>T 5_prime_UTR_variant Exon 1 of 26 ENST00000442250.6 NP_001381857.1
ITGA6NM_000210.4 linkc.-122C>T 5_prime_UTR_variant Exon 1 of 26 ENST00000684293.1 NP_000201.2 P23229-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ITGA6ENST00000442250 linkc.-122C>T 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 26 5 NM_001394928.1 ENSP00000406694.1 P23229-1
ITGA6ENST00000684293 linkc.-122C>T 5_prime_UTR_premature_start_codon_gain_variant Exon 1 of 26 NM_000210.4 ENSP00000508249.1 P23229-2
ITGA6ENST00000442250 linkc.-122C>T 5_prime_UTR_variant Exon 1 of 26 5 NM_001394928.1 ENSP00000406694.1 P23229-1
ITGA6ENST00000684293 linkc.-122C>T 5_prime_UTR_variant Exon 1 of 26 NM_000210.4 ENSP00000508249.1 P23229-2

Frequencies

GnomAD3 genomes
AF:
0.000158
AC:
24
AN:
152202
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00174
Gnomad SAS
AF:
0.00165
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000903
AC:
106
AN:
1174050
Hom.:
1
Cov.:
34
AF XY:
0.000110
AC XY:
62
AN XY:
565710
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000812
Gnomad4 SAS exome
AF:
0.00138
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000206
Gnomad4 OTH exome
AF:
0.000484
GnomAD4 genome
AF:
0.000158
AC:
24
AN:
152310
Hom.:
0
Cov.:
33
AF XY:
0.000188
AC XY:
14
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00174
Gnomad4 SAS
AF:
0.00166
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000108
Hom.:
0
Bravo
AF:
0.000159
Asia WGS
AF:
0.00377
AC:
13
AN:
3464

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Junctional epidermolysis bullosa with pyloric atresia Uncertain:1
Jan 13, 2018
Illumina Laboratory Services, Illumina
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.32
CADD
Benign
18
DANN
Benign
0.96
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs373890886; hg19: chr2-173292395; API