2-172353161-A-G

Variant names:

• chr2-172353161-A-G
• rs4972810
• ENST00000715295.1:c.-369-14610A>G

Variant summary

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

The ENST00000715295.1(ITGA6):​c.-369-14610A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 152,158 control chromosomes in the GnomAD database, including 54,258 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 0.83 (54258 hom., cov: 31)
• Consequence: ITGA6 ENST00000715295.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228
• Publications: 4 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

ENSG00000232555 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000715295.1. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA6	ENST00000715295.1		c.-369-14610A>G		intron	N/A	ENSP00000520448.1
	ENSG00000232555	ENST00000657632.1		n.239-14610A>G		intron	N/A
	ENSG00000232555	ENST00000671082.1		n.862-14610A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.835 AC: 126916 AN: 152038 Hom.: 54210 Cov.: 31

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.899

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.639

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.902

Gnomad OTH AF: 0.838

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

GnomAD4 genome AF: 0.835 AC: 127024 AN: 152158 Hom.: 54258 Cov.: 31 AF XY: 0.824 AC XY: 61303 AN XY: 74364

African (AFR) AF: 0.827 AC: 34320 AN: 41486

American (AMR) AF: 0.816 AC: 12466 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.876 AC: 3039 AN: 3468

East Asian (EAS) AF: 0.251 AC: 1299 AN: 5178

South Asian (SAS) AF: 0.640 AC: 3082 AN: 4818

European-Finnish (FIN) AF: 0.814 AC: 8617 AN: 10580

Middle Eastern (MID) AF: 0.895 AC: 263 AN: 294

European-Non Finnish (NFE) AF: 0.902 AC: 61358 AN: 68026

Other (OTH) AF: 0.833 AC: 1760 AN: 2114

Alfa AF: 0.879 Hom.: 45658

Bravo AF: 0.830

Asia WGS AF: 0.492 AC: 1715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.47
PhyloP100		-0.23

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4972810; hg19: chr2-173217889;