rs12621278

Variant names:

• chr2-172446825-A-G
• rs12621278
• NM_001394928.1:c.183-18714A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001394928.1(ITGA6):​c.183-18714A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0524 in 152,266 control chromosomes in the GnomAD database, including 366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.052 (366 hom., cov: 32)
• Consequence: ITGA6 NM_001394928.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.286
• Publications: 119 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-172446825-A-G is Benign according to our data. Variant chr2-172446825-A-G is described in ClinVar as Benign. ClinVar VariationId is 1599744.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGA6	NM_001394928.1	c.183-18714A>G		intron_variant	Intron 1 of 25	ENST00000442250.6	NP_001381857.1
ITGA6	NM_000210.4	c.183-18714A>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.183-18714A>G		intron_variant	Intron 1 of 25	5	NM_001394928.1	ENSP00000406694.1
ITGA6	ENST00000684293.1	c.183-18714A>G		intron_variant	Intron 1 of 25		NM_000210.4	ENSP00000508249.1

Frequencies

GnomAD3 genomes AF: 0.0524 AC: 7967 AN: 152148 Hom.: 366 Cov.: 32

Gnomad AFR AF: 0.0121

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0563

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.0896

Gnomad FIN AF: 0.0446

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0589

Gnomad OTH AF: 0.0499

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

GnomAD4 genome AF: 0.0524 AC: 7976 AN: 152266 Hom.: 366 Cov.: 32 AF XY: 0.0533 AC XY: 3972 AN XY: 74454

African (AFR) AF: 0.0121 AC: 502 AN: 41578

American (AMR) AF: 0.0565 AC: 864 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0444 AC: 154 AN: 3472

East Asian (EAS) AF: 0.262 AC: 1358 AN: 5178

South Asian (SAS) AF: 0.0895 AC: 432 AN: 4828

European-Finnish (FIN) AF: 0.0446 AC: 473 AN: 10610

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0589 AC: 4006 AN: 68004

Other (OTH) AF: 0.0536 AC: 113 AN: 2108

Alfa AF: 0.0615 Hom.: 1474

Bravo AF: 0.0532

Asia WGS AF: 0.146 AC: 507 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.9
DANN	Benign	0.66
PhyloP100		0.29
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: rs12621278; hg19: chr2-173311553;