2-160101838-GAA-G

Position:

• chr2-160101838-GAA-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000888.5(ITGB6):​c.2269-6_2269-5del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 1,030,676 control chromosomes in the GnomAD database, including 63,724 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (18541 hom., cov: 0)
  • Exomes 𝑓: 0.39 (45183 hom.)
• Consequence: ITGB6 NM_000888.5 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.27

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 2-160101838-GAA-G is Benign according to our data. Variant chr2-160101838-GAA-G is described in ClinVar as [Benign]. Clinvar id is 218474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGB6	NM_000888.5	c.2269-6_2269-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000283249.7	NP_000879.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB6	ENST00000283249.7	c.2269-6_2269-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000888.5	ENSP00000283249	P1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64272 AN: 150172 Hom.: 18482 Cov.: 0

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.397

GnomAD3 exomes AF: 0.461 AC: 74926 AN: 162560 Hom.: 12906 AF XY: 0.448 AC XY: 38671 AN XY: 86300

Gnomad AFR exome AF: 0.805

Gnomad AMR exome AF: 0.592

Gnomad ASJ exome AF: 0.431

Gnomad EAS exome AF: 0.538

Gnomad SAS exome AF: 0.458

Gnomad FIN exome AF: 0.349

Gnomad NFE exome AF: 0.370

Gnomad OTH exome AF: 0.437

GnomAD4 exome AF: 0.393 AC: 345957 AN: 880392 Hom.: 45183 AF XY: 0.391 AC XY: 174717 AN XY: 446512

Gnomad4 AFR exome AF: 0.806

Gnomad4 AMR exome AF: 0.591

Gnomad4 ASJ exome AF: 0.408

Gnomad4 EAS exome AF: 0.533

Gnomad4 SAS exome AF: 0.443

Gnomad4 FIN exome AF: 0.346

Gnomad4 NFE exome AF: 0.355

Gnomad4 OTH exome AF: 0.420

GnomAD4 genome AF: 0.428 AC: 64385 AN: 150284 Hom.: 18541 Cov.: 0 AF XY: 0.427 AC XY: 31305 AN XY: 73290

Gnomad4 AFR AF: 0.809

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.361

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.398

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Apr 17, 2015

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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

Other links and lift over

dbSNP: rs5835793; hg19: chr2-160958349;