2-172440802-G-A

Position:

• chr2-172440802-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394928.1(ITGA6):​c.182+12832G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0943 in 152,100 control chromosomes in the GnomAD database, including 1,570 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.094 (1570 hom., cov: 32)
• Consequence: ITGA6 NM_001394928.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGA6	NM_000210.4	c.182+12832G>A		intron_variant		ENST00000684293.1
ITGA6	NM_001394928.1	c.182+12832G>A		intron_variant		ENST00000442250.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA6	ENST00000442250.6	c.182+12832G>A		intron_variant		5	NM_001394928.1
ITGA6	ENST00000684293.1	c.182+12832G>A		intron_variant			NM_000210.4	P3

Frequencies

GnomAD3 genomes AF: 0.0943 AC: 14329 AN: 151982 Hom.: 1570 Cov.: 32

Gnomad AFR AF: 0.0322

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.0449

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0566

Gnomad OTH AF: 0.0957

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

GnomAD4 genome AF: 0.0943 AC: 14341 AN: 152100 Hom.: 1570 Cov.: 32 AF XY: 0.108 AC XY: 8034 AN XY: 74332

Gnomad4 AFR AF: 0.0324

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.0449

Gnomad4 EAS AF: 0.516

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.0566

Gnomad4 OTH AF: 0.0999

Alfa AF: 0.0805 Hom.: 110

Bravo AF: 0.0859

Asia WGS AF: 0.353 AC: 1226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.64

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: rs10497381; hg19: chr2-173305530;