2-172464986-A-G

Variant names:

• chr2-172464986-A-G
• rs12620581
• NM_001394928.1:c.183-553A>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.183-553A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,076 control chromosomes in the GnomAD database, including 4,175 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 0.19 (4175 hom., cov: 32)
• Consequence: ITGA6 NM_001394928.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.269
• 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]

PDK1-AS1 (HGNC:40441): (PDK1 and ITGA6 antisense RNA 1)

ITGA6-AS1 (HGNC:40308): (ITGA6 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA6	NM_001394928.1	c.183-553A>G		intron_variant	Intron 1 of 25	ENST00000442250.6	NP_001381857.1
ITGA6	NM_000210.4	c.183-553A>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.183-553A>G		intron_variant	Intron 1 of 25	5	NM_001394928.1	ENSP00000406694.1
ITGA6	ENST00000684293.1	c.183-553A>G		intron_variant	Intron 1 of 25		NM_000210.4	ENSP00000508249.1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29284 AN: 151958 Hom.: 4157 Cov.: 32

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.0717

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0973

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.193 AC: 29358 AN: 152076 Hom.: 4175 Cov.: 32 AF XY: 0.205 AC XY: 15257 AN XY: 74324

African (AFR) AF: 0.246 AC: 10203 AN: 41476

American (AMR) AF: 0.249 AC: 3801 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0717 AC: 249 AN: 3472

East Asian (EAS) AF: 0.764 AC: 3946 AN: 5162

South Asian (SAS) AF: 0.296 AC: 1426 AN: 4818

European-Finnish (FIN) AF: 0.250 AC: 2629 AN: 10536

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0973 AC: 6619 AN: 68006

Other (OTH) AF: 0.173 AC: 366 AN: 2114

Alfa AF: 0.125 Hom.: 393

Bravo AF: 0.198

Asia WGS AF: 0.486 AC: 1686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.2
DANN	Benign	0.75
PhyloP100		0.27
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: rs12620581; hg19: chr2-173329714;