rs2290083

Positions:

• chr2-186669014-T-C
• chr2-186669014-T-G

Variant summary

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

The NM_002210.5(ITGAV):​c.2592+94T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 1,174,858 control chromosomes in the GnomAD database, including 89,788 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 0.37 (10924 hom., cov: 32)
  • Exomes 𝑓: 0.38 (78864 hom.)
• Consequence: ITGAV NM_002210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.818

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGAV	NM_002210.5	c.2592+94T>C		intron_variant		ENST00000261023.8
ITGAV	NM_001144999.3	c.2454+94T>C		intron_variant
ITGAV	NM_001145000.3	c.2484+94T>C		intron_variant
ITGAV	XM_047444225.1	c.1749+94T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGAV	ENST00000261023.8	c.2592+94T>C		intron_variant		1	NM_002210.5	P2
	ENST00000453665.1	n.132-8433A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56126 AN: 151890 Hom.: 10923 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.372

GnomAD4 exome AF: 0.383 AC: 392096 AN: 1022850 Hom.: 78864 AF XY: 0.382 AC XY: 196227 AN XY: 513884

Gnomad4 AFR exome AF: 0.289

Gnomad4 AMR exome AF: 0.408

Gnomad4 ASJ exome AF: 0.402

Gnomad4 EAS exome AF: 0.758

Gnomad4 SAS exome AF: 0.306

Gnomad4 FIN exome AF: 0.438

Gnomad4 NFE exome AF: 0.370

Gnomad4 OTH exome AF: 0.381

GnomAD4 genome AF: 0.369 AC: 56146 AN: 152008 Hom.: 10924 Cov.: 32 AF XY: 0.376 AC XY: 27900 AN XY: 74300

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.736

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.369

Alfa AF: 0.365 Hom.: 1277

Bravo AF: 0.365

Asia WGS AF: 0.454 AC: 1581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.2
DANN	Benign	0.76

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: rs2290083; hg19: chr2-187533741; COSMIC: COSV53713936; COSMIC: COSV53713936;