2-172504157-AAAG-A

Variant names:

• chr2-172504157-AAAG-A
• rs863223349
• NM_001394928.1:c.3303_3305delAGA

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PM4_Supporting PP5_Moderate

The NM_001394928.1(ITGA6):​c.3303_3305delAGA​(p.Glu1102del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITGA6 NM_001394928.1 disruptive_inframe_deletion
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 9.60
• Publications: 1 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)

PDK1-AS1 (HGNC:40441): (PDK1 and ITGA6 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001394928.1. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 2-172504157-AAAG-A is Pathogenic according to our data. Variant chr2-172504157-AAAG-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 208387.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394928.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA6	NM_001394928.1	MANE Plus Clinical	c.3303_3305delAGA	p.Glu1102del	disruptive_inframe_deletion	Exon 26 of 26	NP_001381857.1
	ITGA6	NM_000210.4	MANE Select	c.*94_*96delAGA		3_prime_UTR	Exon 26 of 26	NP_000201.2
	ITGA6	NM_001079818.3		c.3186_3188delAGA	p.Glu1063del	disruptive_inframe_deletion	Exon 25 of 25	NP_001073286.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA6	ENST00000442250.6	TSL:5 MANE Plus Clinical	c.3303_3305delAGA	p.Glu1102del	disruptive_inframe_deletion	Exon 26 of 26	ENSP00000406694.1
	ITGA6	ENST00000684293.1	MANE Select	c.*94_*96delAGA		3_prime_UTR	Exon 26 of 26	ENSP00000508249.1
	ITGA6	ENST00000264107.12	TSL:1	c.*94_*96delAGA		3_prime_UTR	Exon 26 of 26	ENSP00000264107.8

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Childhood-onset schizophrenia Pathogenic:1

Jan 01, 2014

Dr. Guy Rouleau's laboratory, McGill University

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.6
Mutation Taster		=31/69	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs863223349; hg19: chr2-173368885;