2-172487779-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000210.4(ITGA6):c.2296G>T(p.Asp766Tyr) 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_000210.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.86

Publications

15 publications found

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:

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

ITGA6-AS1 links:

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

PDK1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 332374.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0787 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ITGA6	NM_001394928.1	MANE Plus Clinical	c.2413G>T	p.Asp805Tyr	missense	Exon 18 of 26	NP_001381857.1
ITGA6	NM_000210.4	MANE Select	c.2296G>T	p.Asp766Tyr	missense	Exon 17 of 26	NP_000201.2
ITGA6	NM_001079818.3		c.2296G>T	p.Asp766Tyr	missense	Exon 17 of 25	NP_001073286.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ITGA6	ENST00000442250.6	TSL:5 MANE Plus Clinical	c.2413G>T	p.Asp805Tyr	missense	Exon 18 of 26	ENSP00000406694.1
ITGA6	ENST00000684293.1	MANE Select	c.2296G>T	p.Asp766Tyr	missense	Exon 17 of 26	ENSP00000508249.1
ITGA6	ENST00000264107.12	TSL:1	c.2296G>T	p.Asp766Tyr	missense	Exon 17 of 26	ENSP00000264107.8

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

GnomAD2 exomes

AF:

0.00607

AC:

1524

AN:

250910

AF XY:

0.00444

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 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

African (AFR)

AF:

0.0834

AC:

2782

AN:

33356

American (AMR)

AF:

0.00411

AC:

184

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.000128

AC:

AN:

86206

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00312

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000739

AC:

AN:

1109826

Other (OTH)

AF:

0.00605

AC:

365

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

186

371

557

742

928

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

172

258

344

430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0235

AC:

3571

AN:

152150

Hom.:

145

Cov.:

AF XY:

0.0222

AC XY:

1653

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0810

AC:

3361

AN:

41492

American (AMR)

AF:

0.00949

AC:

145

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000323

AC:

AN:

68014

Other (OTH)

AF:

0.0199

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

157

314

471

628

785

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00766

Hom.:

183

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

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

ITGA6-related disorder (1)

Junctional epidermolysis bullosa with pyloric atresia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.65

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

MetaRNN

Benign

0.0038

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

PhyloP100

4.9

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-4.3

REVEL

Benign

0.27

Sift

Uncertain

0.014

Sift4G

Uncertain

0.0060

Polyphen

0.95

Vest4

0.54

MVP

0.66

MPC

0.68

ClinPred

0.044

GERP RS

6.1

PromoterAI

-0.016

Neutral

(source)

Varity_R

0.43

gMVP

0.59

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over