chr2-172487779-G-T

Position:

chr2-172487779-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001394928.1(ITGA6):c.2413G>T(p.Asp805Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00435 in 1,611,508 control chromosomes in the GnomAD database, including 267 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 145 hom., cov: 33)

Exomes 𝑓: 0.0024 ( 122 hom. )

Consequence

ITGA6
NM_001394928.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.86

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038056672).

BP6

Variant 2-172487779-G-T is Benign according to our data. Variant chr2-172487779-G-T is described in ClinVar as [Benign]. Clinvar id is 332374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-172487779-G-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ITGA6	NM_001394928.1 linkuse as main transcript	c.2413G>T	p.Asp805Tyr	missense_variant	18/26	ENST00000442250.6	NP_001381857.1
ITGA6	NM_000210.4 linkuse as main transcript	c.2296G>T	p.Asp766Tyr	missense_variant	17/26	ENST00000684293.1	NP_000201.2
LOC124900513	XR_007087304.1 linkuse as main transcript	n.704-6758C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA6	ENST00000442250.6 linkuse as main transcript	c.2413G>T	p.Asp805Tyr	missense_variant	18/26	5	NM_001394928.1	ENSP00000406694		P23229-1
ITGA6	ENST00000684293.1 linkuse as main transcript	c.2296G>T	p.Asp766Tyr	missense_variant	17/26		NM_000210.4	ENSP00000508249	P3	P23229-2
PDK1-AS1	ENST00000442417.5 linkuse as main transcript	n.769-6758C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0235

AC:

3573

AN:

152032

Hom.:

145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0813

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00957

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.00607

AC:

1524

AN:

250910

Hom.:

AF XY:

0.00444

AC XY:

602

AN XY:

135644

show subpopulations

Gnomad AFR exome

AF:

0.0842

Gnomad AMR exome

AF:

0.00356

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00236

AC:

3442

AN:

1459358

Hom.:

122

Cov.:

AF XY:

0.00195

AC XY:

1415

AN XY:

726192

show subpopulations

Gnomad4 AFR exome

AF:

0.0834

Gnomad4 AMR exome

AF:

0.00411

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000739

Gnomad4 OTH exome

AF:

0.00605

GnomAD4 genome

AF:

0.0235

AC:

3571

AN:

152150

Hom.:

145

Cov.:

AF XY:

0.0222

AC XY:

1653

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0810

Gnomad4 AMR

AF:

0.00949

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.0199

Alfa

AF:

0.00335

Hom.:

Bravo

AF:

0.0274

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0833

AC:

367

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00772

AC:

937

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000474

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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Junctional epidermolysis bullosa with pyloric atresia

Benign:1

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. -

ITGA6-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

.;.;T;.;.

Eigen

Uncertain

0.65

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D;D;D;D

MetaRNN

Benign

0.0038

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

.;.;M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-4.3

D;D;D;D;D

REVEL

Benign

0.27

Sift

Uncertain

0.014

D;D;D;D;D

Sift4G

Uncertain

0.0060

D;D;D;D;D

Polyphen

0.95

.;P;.;.;.

Vest4

0.54

MVP

0.66

MPC

0.68

ClinPred

0.044

GERP RS

6.1

Varity_R

0.43

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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