2-172240751-T-C

Variant names:

• chr2-172240751-T-C
• rs10930538
• ENST00000715295.1:c.-536+6494T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000715295.1(ITGA6):​c.-536+6494T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 152,068 control chromosomes in the GnomAD database, including 23,860 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (23860 hom., cov: 32)
• Consequence: ITGA6 ENST00000715295.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258
• Publications: 7 publications found

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]

DLX2-DT (HGNC:50638): (DLX2 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA6	ENST00000715295.1	c.-536+6494T>C		intron_variant	Intron 1 of 27			ENSP00000520448.1
DLX2-DT	ENST00000662340.1	n.213-57446T>C		intron_variant	Intron 2 of 3
DLX2-DT	ENST00000667725.1	n.242-57446T>C		intron_variant	Intron 2 of 4
DLX2-DT	ENST00000715288.1	n.457-57452T>C		intron_variant	Intron 3 of 5

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81855 AN: 151950 Hom.: 23865 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.575

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.538 AC: 81872 AN: 152068 Hom.: 23860 Cov.: 32 AF XY: 0.539 AC XY: 40080 AN XY: 74328

African (AFR) AF: 0.298 AC: 12365 AN: 41464

American (AMR) AF: 0.571 AC: 8730 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2236 AN: 3468

East Asian (EAS) AF: 0.655 AC: 3380 AN: 5164

South Asian (SAS) AF: 0.529 AC: 2544 AN: 4812

European-Finnish (FIN) AF: 0.620 AC: 6551 AN: 10568

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.648 AC: 44023 AN: 67988

Other (OTH) AF: 0.571 AC: 1205 AN: 2110

Alfa AF: 0.602 Hom.: 94304

Bravo AF: 0.525

Asia WGS AF: 0.536 AC: 1866 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.7
DANN	Benign	0.82
PhyloP100		0.26

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10930538; hg19: chr2-173105479;