chr2-172491230-G-A

Position:

chr2-172491230-G-A

Variant summary

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

The NM_001394928.1(ITGA6):c.2905G>A(p.Val969Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00576 in 1,605,338 control chromosomes in the GnomAD database, including 440 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 216 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 224 hom. )

Consequence

ITGA6
NM_001394928.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.06

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=0.0015976727).

BP6

Variant 2-172491230-G-A is Benign according to our data. Variant chr2-172491230-G-A is described in ClinVar as [Benign]. Clinvar id is 332379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.104 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.2905G>A	p.Val969Met	missense_variant	23/26	ENST00000442250.6	NP_001381857.1
ITGA6	NM_000210.4 linkuse as main transcript	c.2788G>A	p.Val930Met	missense_variant	22/26	ENST00000684293.1	NP_000201.2
LOC124900513	XR_007087304.1 linkuse as main transcript	n.703+4145C>T		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.2905G>A	p.Val969Met	missense_variant	23/26	5	NM_001394928.1	ENSP00000406694		P23229-1
ITGA6	ENST00000684293.1 linkuse as main transcript	c.2788G>A	p.Val930Met	missense_variant	22/26		NM_000210.4	ENSP00000508249	P3	P23229-2
PDK1-AS1	ENST00000442417.5 linkuse as main transcript	n.768+4145C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0301

AC:

4580

AN:

152084

Hom.:

217

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00851

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.00849

AC:

2133

AN:

251342

Hom.:

107

AF XY:

0.00609

AC XY:

827

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.116

Gnomad AMR exome

AF:

0.00489

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000396

Gnomad OTH exome

AF:

0.00343

GnomAD4 exome

AF:

0.00319

AC:

4640

AN:

1453136

Hom.:

224

Cov.:

AF XY:

0.00275

AC XY:

1992

AN XY:

723636

show subpopulations

Gnomad4 AFR exome

AF:

0.108

Gnomad4 AMR exome

AF:

0.00577

Gnomad4 ASJ exome

AF:

0.000307

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000197

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.000262

Gnomad4 OTH exome

AF:

0.00741

GnomAD4 genome

AF:

0.0302

AC:

4599

AN:

152202

Hom.:

216

Cov.:

AF XY:

0.0286

AC XY:

2129

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.106

Gnomad4 AMR

AF:

0.00843

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.00606

Hom.:

Bravo

AF:

0.0351

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.109

AC:

481

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.0103

AC:

1256

Asia WGS

AF:

0.00953

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 27, 2020	- -
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: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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.043

.;.;T;.;.;T

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.68

T;T;T;T;T;T

MetaRNN

Benign

0.0016

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

.;.;L;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

0.34

N;N;N;N;N;N

REVEL

Benign

0.054

Sift

Benign

0.12

T;T;T;T;T;T

Sift4G

Benign

0.19

T;T;T;T;T;T

Polyphen

0.63

.;P;.;.;.;.

Vest4

0.23

MPC

0.42

ClinPred

0.0029

GERP RS

2.0

Varity_R

0.020

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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