2-186613773-A-G

Position:

• chr2-186613773-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002210.5(ITGAV):​c.317-8566A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 151,980 control chromosomes in the GnomAD database, including 37,439 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 0.70 (37439 hom., cov: 32)
• Consequence: ITGAV NM_002210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0680

Genes affected

ITGAV (HGNC:6150): (integrin subunit alpha V) The product of this gene belongs to the integrin alpha chain family. Integrins are heterodimeric integral membrane proteins composed of an alpha subunit and a beta subunit that function in cell surface adhesion and signaling. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha V subunit. This subunit associates with beta 1, beta 3, beta 5, beta 6 and beta 8 subunits. The heterodimer consisting of alpha V and beta 3 subunits is also known as the vitronectin receptor. This integrin may regulate angiogenesis and cancer progression. Alternative splicing results in multiple transcript variants. Note that the integrin alpha 5 and integrin alpha V subunits are encoded by distinct genes. [provided by RefSeq, Oct 2015]

ITGAV (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGAV	NM_002210.5	c.317-8566A>G		intron_variant		ENST00000261023.8	NP_002201.2
ITGAV	NM_001145000.3	c.317-8566A>G		intron_variant			NP_001138472.2
ITGAV	NM_001144999.3	c.179-8566A>G		intron_variant			NP_001138471.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGAV	ENST00000261023.8	c.317-8566A>G		intron_variant		1	NM_002210.5	ENSP00000261023.3

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106061 AN: 151864 Hom.: 37419 Cov.: 32

Gnomad AFR AF: 0.579

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.852

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.751

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.741

Gnomad OTH AF: 0.715

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

GnomAD4 genome AF: 0.698 AC: 106131 AN: 151980 Hom.: 37439 Cov.: 32 AF XY: 0.699 AC XY: 51932 AN XY: 74276

Gnomad4 AFR AF: 0.579

Gnomad4 AMR AF: 0.719

Gnomad4 ASJ AF: 0.713

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.744

Gnomad4 FIN AF: 0.751

Gnomad4 NFE AF: 0.741

Gnomad4 OTH AF: 0.713

Alfa AF: 0.616 Hom.: 1780

Bravo AF: 0.692

Asia WGS AF: 0.769 AC: 2659 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs3768780; hg19: chr2-187478500;