rs10497381

Variant names:

• chr2-172440802-G-A
• rs10497381
• NM_001394928.1:c.182+12832G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-172440802-G-A
• chr2-172440802-G-C
• chr2-172440802-G-T

Variant summary

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

The NM_000210.4(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_000210.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116
• 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]

ITGA6 Gene-Disease associations (from GenCC):

• junctional epidermolysis bullosa with pyloric atresia

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000210.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA6	NM_001394928.1	MANE Plus Clinical	c.182+12832G>A		intron	N/A	NP_001381857.1	P23229-1
	ITGA6	NM_000210.4	MANE Select	c.182+12832G>A		intron	N/A	NP_000201.2	P23229-2
	ITGA6	NM_001079818.3		c.182+12832G>A		intron	N/A	NP_001073286.1	P23229-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA6	ENST00000442250.6	TSL:5 MANE Plus Clinical	c.182+12832G>A		intron	N/A	ENSP00000406694.1	P23229-1
	ITGA6	ENST00000684293.1	MANE Select	c.182+12832G>A		intron	N/A	ENSP00000508249.1	P23229-2
	ITGA6	ENST00000264107.12	TSL:1	c.182+12832G>A		intron	N/A	ENSP00000264107.8	A0A8C8KBL6

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

African (AFR) AF: 0.0324 AC: 1345 AN: 41502

American (AMR) AF: 0.161 AC: 2466 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0449 AC: 156 AN: 3472

East Asian (EAS) AF: 0.516 AC: 2664 AN: 5162

South Asian (SAS) AF: 0.234 AC: 1123 AN: 4808

European-Finnish (FIN) AF: 0.231 AC: 2437 AN: 10560

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0566 AC: 3850 AN: 67992

Other (OTH) AF: 0.0999 AC: 211 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.64
PhyloP100		-0.12
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: rs10497381; hg19: chr2-173305530;