rs6717347

Variant names:

• chr2-172252782-G-T
• rs6717347
• ENST00000715295.1:c.-536+18525G>T

Variant summary

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

The ENST00000715295.1(ITGA6):​c.-536+18525G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 152,046 control chromosomes in the GnomAD database, including 8,538 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 0.32 (8538 hom., cov: 33)
• Consequence: ITGA6 ENST00000715295.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.884
• Publications: 2 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)

ENSG00000295985 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC107985960	XR_001739773.3	n.2208+149G>T		intron_variant	Intron 1 of 5
LOC107985960	XR_001739775.3	n.2208+149G>T		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGA6	ENST00000715295.1	c.-536+18525G>T		intron_variant	Intron 1 of 27			ENSP00000520448.1
DLX2-DT	ENST00000662340.1	n.213-45415G>T		intron_variant	Intron 2 of 3
DLX2-DT	ENST00000667725.1	n.242-45415G>T		intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48948 AN: 151928 Hom.: 8534 Cov.: 33

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.255

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.322 AC: 48971 AN: 152046 Hom.: 8538 Cov.: 33 AF XY: 0.324 AC XY: 24078 AN XY: 74320

African (AFR) AF: 0.470 AC: 19475 AN: 41462

American (AMR) AF: 0.283 AC: 4336 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1032 AN: 3468

East Asian (EAS) AF: 0.297 AC: 1535 AN: 5162

South Asian (SAS) AF: 0.301 AC: 1453 AN: 4820

European-Finnish (FIN) AF: 0.272 AC: 2874 AN: 10578

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17355 AN: 67950

Other (OTH) AF: 0.294 AC: 619 AN: 2108

Alfa AF: 0.270 Hom.: 10918

Bravo AF: 0.328

Asia WGS AF: 0.274 AC: 952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.43
PhyloP100		-0.88

Splicing

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

Other links and lift over

dbSNP: rs6717347; hg19: chr2-173117510;