rs863223349

chr2-172504157-AAAG-A

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4_Supporting PP5_Moderate

The NM_001394928.1(ITGA6):c.3303_3305del(p.Glu1102del) variant causes a 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 inframe_deletion
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 9.60

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]

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

LOC124900513 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 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 id is 208387.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA6	NM_001394928.1	c.3303_3305del	p.Glu1102del	inframe_deletion	26/26	ENST00000442250.6
ITGA6	NM_000210.4	c.*94_*96del		3_prime_UTR_variant	26/26	ENST00000684293.1
LOC124900513	XR_007087304.1	n.561+8174_561+8176del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA6	ENST00000442250.6	c.3303_3305del	p.Glu1102del	inframe_deletion	26/26	5	NM_001394928.1
ITGA6	ENST00000684293.1	c.*94_*96del		3_prime_UTR_variant	26/26		NM_000210.4	P3
PDK1-AS1	ENST00000442417.5	n.626+8174_626+8176del		intron_variant, non_coding_transcript_variant		3

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

Likely pathogenic, criteria provided, single submitter

research

Dr. Guy Rouleau's laboratory, McGill University

Jan 01, 2014

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Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs863223349; hg19: chr2-173368885;