2-172427871-C-T

Variant names:

• chr2-172427871-C-T
• NM_001394928.1:c.83C>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_000210.4(ITGA6):​c.83C>T​(p.Thr28Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ITGA6 NM_000210.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.27

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]

ENSG00000226963 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.804

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA6	NM_001394928.1	c.83C>T	p.Thr28Ile	missense_variant	Exon 1 of 26	ENST00000442250.6	NP_001381857.1
ITGA6	NM_000210.4	c.83C>T	p.Thr28Ile	missense_variant	Exon 1 of 26	ENST00000684293.1	NP_000201.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA6	ENST00000442250.6	c.83C>T	p.Thr28Ile	missense_variant	Exon 1 of 26	5	NM_001394928.1	ENSP00000406694.1
ITGA6	ENST00000684293.1	c.83C>T	p.Thr28Ile	missense_variant	Exon 1 of 26		NM_000210.4	ENSP00000508249.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Epidermolysis bullosa, junctional 6, with pyloric atresia Uncertain:1

Mar 14, 2024

Fulgent Genetics, Fulgent Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	.;T;.;.
Eigen	Uncertain	0.30
Eigen_PC	Benign	0.22
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.76	T;T;T;T
M_CAP	Pathogenic	0.82	D
MetaRNN	Pathogenic	0.80	D;D;D;D
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.4	M;M;M;M
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-2.8	D;D;D;D
REVEL	Benign	0.22
Sift	Benign	0.060	T;T;T;T
Sift4G	Benign	0.13	T;T;T;T
Polyphen		0.97	D;.;.;.
Vest4		0.58
MutPred		0.49		Loss of phosphorylation at T28 (P = 0.0405);Loss of phosphorylation at T28 (P = 0.0405);Loss of phosphorylation at T28 (P = 0.0405);Loss of phosphorylation at T28 (P = 0.0405);
MVP		0.69
MPC		1.3
ClinPred		0.98	D
GERP RS		4.2
Varity_R		0.33
gMVP		0.82

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-173292599;