Variant chr2-160101834-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_000888.5(ITGB6):c.2269G>A(p.Gly757Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000218 in 1,374,302 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 28)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

ITGB6
NM_000888.5 missense, splice_region

Scores

Splicing: ADA: 0.9982

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.22

Variant links:

Genes affected

ITGB6 (HGNC:6161): (integrin subunit beta 6) This gene encodes a protein that is a member of the integrin superfamily. Members of this family are adhesion receptors that function in signaling from the extracellular matrix to the cell. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. The encoded protein forms a dimer with an alpha v chain and this heterodimer can bind to ligands like fibronectin and transforming growth factor beta 1. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ITGB6 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. Scorers claiming Uncertain: max_spliceai. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGB6	NM_000888.5 linkuse as main transcript	c.2269G>A	p.Gly757Arg	missense_variant, splice_region_variant	15/15	ENST00000283249.7	NP_000879.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB6	ENST00000283249.7 linkuse as main transcript	c.2269G>A	p.Gly757Arg	missense_variant, splice_region_variant	15/15	1	NM_000888.5	ENSP00000283249	P1	P18564-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000166

AC:

AN:

120796

Hom.:

AF XY:

0.0000146

AC XY:

AN XY:

68560

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000109

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000160

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000218

AC:

AN:

1374302

Hom.:

Cov.:

AF XY:

0.00000291

AC XY:

AN XY:

687644

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000502

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.58e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000249

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 24, 2024

The c.2269G>A (p.G757R) alteration is located in exon 15 (coding exon 15) of the ITGB6 gene. This alteration results from a G to A substitution at nucleotide position 2269, causing the glycine (G) at amino acid position 757 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.61

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.79

D;.;.;.;D

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.81

.;T;T;D;T

M_CAP

Pathogenic

0.31

MetaRNN

Uncertain

0.55

D;D;D;D;D

MetaSVM

Uncertain

0.76

MutationAssessor

Uncertain

2.6

M;.;.;.;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Uncertain

-3.5

D;.;D;D;D

REVEL

Pathogenic

0.72

Sift

Uncertain

0.0010

D;.;D;D;D

Sift4G

Uncertain

0.0070

D;D;D;D;D

Polyphen

0.99

D;.;D;.;D

Vest4

0.43

MutPred

0.68

Gain of MoRF binding (P = 0.0249);.;.;.;Gain of MoRF binding (P = 0.0249);

MVP

0.81

MPC

0.20

ClinPred

0.94

GERP RS

5.6

Varity_R

0.63

gMVP

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.81

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.22

Position offset: 0

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