rs2293649

Positions:

chr2-172487375-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001394928.1(ITGA6):c.2199C>T(p.Asp733=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,612,818 control chromosomes in the GnomAD database, including 54,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5321 hom., cov: 33)

Exomes 𝑓: 0.24 ( 49153 hom. )

Consequence

ITGA6
NM_001394928.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.04

Variant links:

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 links:

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

PDK1-AS1 links:

LOC124900513 (HGNC:):

LOC124900513 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 2-172487375-C-T is Benign according to our data. Variant chr2-172487375-C-T is described in ClinVar as [Benign]. Clinvar id is 332369.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-172487375-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ITGA6	NM_001394928.1 linkuse as main transcript	c.2199C>T	p.Asp733=	synonymous_variant	16/26	ENST00000442250.6
ITGA6	NM_000210.4 linkuse as main transcript	c.2082C>T	p.Asp694=	synonymous_variant	15/26	ENST00000684293.1
LOC124900513	XR_007087304.1 linkuse as main transcript	n.704-6354G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGA6	ENST00000442250.6 linkuse as main transcript	c.2199C>T	p.Asp733=	synonymous_variant	16/26	5	NM_001394928.1		P23229-1
ITGA6	ENST00000684293.1 linkuse as main transcript	c.2082C>T	p.Asp694=	synonymous_variant	15/26		NM_000210.4	P3	P23229-2
PDK1-AS1	ENST00000442417.5 linkuse as main transcript	n.769-6354G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38456

AN:

152008

Hom.:

5314

Cov.:

show subpopulations

Gnomad AFR

AF:

0.213

Gnomad AMI

AF:

0.208

Gnomad AMR

AF:

0.339

Gnomad ASJ

AF:

0.256

Gnomad EAS

AF:

0.551

Gnomad SAS

AF:

0.419

Gnomad FIN

AF:

0.352

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.209

Gnomad OTH

AF:

0.253

GnomAD3 exomes

AF:

0.306

AC:

76760

AN:

251228

Hom.:

13582

AF XY:

0.303

AC XY:

41186

AN XY:

135774

show subpopulations

Gnomad AFR exome

AF:

0.212

Gnomad AMR exome

AF:

0.430

Gnomad ASJ exome

AF:

0.254

Gnomad EAS exome

AF:

0.540

Gnomad SAS exome

AF:

0.416

Gnomad FIN exome

AF:

0.345

Gnomad NFE exome

AF:

0.212

Gnomad OTH exome

AF:

0.273

GnomAD4 exome

AF:

0.244

AC:

356353

AN:

1460692

Hom.:

49153

Cov.:

AF XY:

0.248

AC XY:

180531

AN XY:

726742

show subpopulations

Gnomad4 AFR exome

AF:

0.218

Gnomad4 AMR exome

AF:

0.423

Gnomad4 ASJ exome

AF:

0.255

Gnomad4 EAS exome

AF:

0.569

Gnomad4 SAS exome

AF:

0.406

Gnomad4 FIN exome

AF:

0.337

Gnomad4 NFE exome

AF:

0.208

Gnomad4 OTH exome

AF:

0.262

GnomAD4 genome

AF:

0.253

AC:

38495

AN:

152126

Hom.:

5321

Cov.:

AF XY:

0.265

AC XY:

19687

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.213

Gnomad4 AMR

AF:

0.340

Gnomad4 ASJ

AF:

0.256

Gnomad4 EAS

AF:

0.551

Gnomad4 SAS

AF:

0.417

Gnomad4 FIN

AF:

0.352

Gnomad4 NFE

AF:

0.209

Gnomad4 OTH

AF:

0.257

Alfa

AF:

0.226

Hom.:

6744

Bravo

AF:

0.252

Asia WGS

AF:

0.475

AC:

1649

AN:

3478

EpiCase

AF:

0.218

EpiControl

AF:

0.209

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Junctional epidermolysis bullosa with pyloric atresia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

0.99

DANN

Benign

0.83

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over