chr2-172435945-A-G

Variant names:

• chr2-172435945-A-G
• rs13027811
• NM_001394928.1:c.182+7975A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394928.1(ITGA6):​c.182+7975A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0766 in 152,176 control chromosomes in the GnomAD database, including 510 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 0.077 (510 hom., cov: 31)
• Consequence: ITGA6 NM_001394928.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.05
• Publications: 8 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 Gene-Disease associations (from GenCC):

• junctional epidermolysis bullosa with pyloric atresia

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• epidermolysis bullosa, junctional 6, with pyloric atresia

  Inheritance: AD Classification: LIMITED Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA6	NM_001394928.1	c.182+7975A>G		intron_variant	Intron 1 of 25	ENST00000442250.6	NP_001381857.1
ITGA6	NM_000210.4	c.182+7975A>G		intron_variant	Intron 1 of 25	ENST00000684293.1	NP_000201.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA6	ENST00000442250.6	c.182+7975A>G		intron_variant	Intron 1 of 25	5	NM_001394928.1	ENSP00000406694.1
ITGA6	ENST00000684293.1	c.182+7975A>G		intron_variant	Intron 1 of 25		NM_000210.4	ENSP00000508249.1

Frequencies

GnomAD3 genomes AF: 0.0767 AC: 11660 AN: 152058 Hom.: 510 Cov.: 31

Gnomad AFR AF: 0.0568

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0820

Gnomad ASJ AF: 0.0888

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0293

Gnomad FIN AF: 0.0407

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0890

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

GnomAD4 genome AF: 0.0766 AC: 11654 AN: 152176 Hom.: 510 Cov.: 31 AF XY: 0.0713 AC XY: 5302 AN XY: 74402

African (AFR) AF: 0.0567 AC: 2352 AN: 41516

American (AMR) AF: 0.0819 AC: 1252 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0888 AC: 308 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.0289 AC: 139 AN: 4808

European-Finnish (FIN) AF: 0.0407 AC: 432 AN: 10608

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6845 AN: 67992

Other (OTH) AF: 0.0876 AC: 185 AN: 2112

Alfa AF: 0.0933 Hom.: 1080

Bravo AF: 0.0809

Asia WGS AF: 0.0170 AC: 58 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.4
DANN	Benign	0.74
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs13027811; hg19: chr2-173300673;