2-172465519-T-G

Variant names:

• chr2-172465519-T-G
• NM_001394928.1:c.183-20T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000210.4(ITGA6):​c.183-20T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ITGA6 NM_000210.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.871
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 2-172465519-T-G is Benign according to our data. Variant chr2-172465519-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2834514.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000210.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA6	NM_001394928.1	MANE Plus Clinical	c.183-20T>G		intron	N/A	NP_001381857.1	P23229-1
	ITGA6	NM_000210.4	MANE Select	c.183-20T>G		intron	N/A	NP_000201.2	P23229-2
	ITGA6	NM_001079818.3		c.183-20T>G		intron	N/A	NP_001073286.1	P23229-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA6	ENST00000442250.6	TSL:5 MANE Plus Clinical	c.183-20T>G		intron	N/A	ENSP00000406694.1	P23229-1
	ITGA6	ENST00000684293.1	MANE Select	c.183-20T>G		intron	N/A	ENSP00000508249.1	P23229-2
	ITGA6	ENST00000264107.12	TSL:1	c.183-20T>G		intron	N/A	ENSP00000264107.8	A0A8C8KBL6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.71
PhyloP100		0.87

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

hg19: chr2-173330247;