2-172253781-G-A

Variant names:

• chr2-172253781-G-A
• rs6721348
• ENST00000715295.1:c.-536+19524G>A

Variant summary

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

The ENST00000715295.1(ITGA6):​c.-536+19524G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.877 in 151,972 control chromosomes in the GnomAD database, including 58,636 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 0.88 (58636 hom., cov: 28)
• Consequence: ITGA6 ENST00000715295.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.359
• Publications: 2 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]

DLX2-DT (HGNC:50638): (DLX2 divergent transcript)

ENSG00000295985 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.904 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.-536+19524G>A		intron	N/A	ENSP00000520448.1
	DLX2-DT	ENST00000662340.1		n.213-44416G>A		intron	N/A
	DLX2-DT	ENST00000667725.1		n.242-44416G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.877 AC: 133185 AN: 151854 Hom.: 58613 Cov.: 28

Gnomad AFR AF: 0.802

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.900

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.881

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.920

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.910

Gnomad OTH AF: 0.883

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

GnomAD4 genome AF: 0.877 AC: 133255 AN: 151972 Hom.: 58636 Cov.: 28 AF XY: 0.879 AC XY: 65339 AN XY: 74298

African (AFR) AF: 0.802 AC: 33183 AN: 41398

American (AMR) AF: 0.900 AC: 13762 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 3179 AN: 3472

East Asian (EAS) AF: 0.882 AC: 4524 AN: 5132

South Asian (SAS) AF: 0.846 AC: 4040 AN: 4778

European-Finnish (FIN) AF: 0.920 AC: 9756 AN: 10604

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.910 AC: 61841 AN: 67984

Other (OTH) AF: 0.878 AC: 1855 AN: 2112

Alfa AF: 0.897 Hom.: 101279

Bravo AF: 0.873

Asia WGS AF: 0.826 AC: 2874 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.79
PhyloP100		-0.36

Splicing

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

Other links and lift over

dbSNP: rs6721348; hg19: chr2-173118509;