2-172465595-C-CGGGAGGGCTGTACA

Variant names:

• chr2-172465595-C-CGGGAGGGCTGTACA
• NM_001394928.1:c.241_254dupGGAGGGCTGTACAG

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_000210.4(ITGA6):​c.241_254dupGGAGGGCTGTACAG​(p.Ser85ArgfsTer50) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ITGA6 NM_000210.4 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: -5.65

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)

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-172465595-C-CGGGAGGGCTGTACA is Pathogenic according to our data. Variant chr2-172465595-C-CGGGAGGGCTGTACA is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3584970.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA6	NM_001394928.1	c.241_254dupGGAGGGCTGTACAG	p.Ser85ArgfsTer50	frameshift_variant	Exon 2 of 26	ENST00000442250.6	NP_001381857.1
ITGA6	NM_000210.4	c.241_254dupGGAGGGCTGTACAG	p.Ser85ArgfsTer50	frameshift_variant	Exon 2 of 26	ENST00000684293.1	NP_000201.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA6	ENST00000442250.6	c.241_254dupGGAGGGCTGTACAG	p.Ser85ArgfsTer50	frameshift_variant	Exon 2 of 26	5	NM_001394928.1	ENSP00000406694.1
ITGA6	ENST00000684293.1	c.241_254dupGGAGGGCTGTACAG	p.Ser85ArgfsTer50	frameshift_variant	Exon 2 of 26		NM_000210.4	ENSP00000508249.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

Feb 18, 2024

Fulgent Genetics, Fulgent Genetics

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

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: chr2-173330323;