2-186590551-C-T

Variant names:

• chr2-186590551-C-T
• rs9333287
• NM_002210.5:c.185+28C>T

Variant summary

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

The NM_002210.5(ITGAV):​c.185+28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 1,596,300 control chromosomes in the GnomAD database, including 439,041 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 (37861 hom., cov: 33)
  • Exomes 𝑓: 0.74 (401180 hom.)
• Consequence: ITGAV NM_002210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• Publications: 5 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAV	NM_002210.5	c.185+28C>T		intron_variant	Intron 1 of 29	ENST00000261023.8	NP_002201.2
ITGAV	NM_001145000.3	c.185+28C>T		intron_variant	Intron 1 of 27		NP_001138472.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAV	ENST00000261023.8	c.185+28C>T		intron_variant	Intron 1 of 29	1	NM_002210.5	ENSP00000261023.3

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106710 AN: 151980 Hom.: 37835 Cov.: 33

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.744

Gnomad OTH AF: 0.719

GnomAD2 exomes AF: 0.737 AC: 168154 AN: 228064 AF XY: 0.741

Gnomad AFR exome AF: 0.584

Gnomad AMR exome AF: 0.709

Gnomad ASJ exome AF: 0.731

Gnomad EAS exome AF: 0.860

Gnomad FIN exome AF: 0.755

Gnomad NFE exome AF: 0.744

Gnomad OTH exome AF: 0.747

GnomAD4 exome AF: 0.745 AC: 1075352 AN: 1444204 Hom.: 401180 Cov.: 31 AF XY: 0.744 AC XY: 534495 AN XY: 717956

African (AFR) AF: 0.578 AC: 18831 AN: 32604

American (AMR) AF: 0.714 AC: 30761 AN: 43090

Ashkenazi Jewish (ASJ) AF: 0.730 AC: 18693 AN: 25614

East Asian (EAS) AF: 0.862 AC: 33235 AN: 38572

South Asian (SAS) AF: 0.737 AC: 62431 AN: 84758

European-Finnish (FIN) AF: 0.749 AC: 39420 AN: 52628

Middle Eastern (MID) AF: 0.706 AC: 3060 AN: 4332

European-Non Finnish (NFE) AF: 0.747 AC: 824395 AN: 1103074

Other (OTH) AF: 0.748 AC: 44526 AN: 59532

GnomAD4 genome AF: 0.702 AC: 106782 AN: 152096 Hom.: 37861 Cov.: 33 AF XY: 0.702 AC XY: 52218 AN XY: 74342

African (AFR) AF: 0.586 AC: 24311 AN: 41494

American (AMR) AF: 0.723 AC: 11063 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2475 AN: 3470

East Asian (EAS) AF: 0.851 AC: 4369 AN: 5132

South Asian (SAS) AF: 0.738 AC: 3564 AN: 4828

European-Finnish (FIN) AF: 0.752 AC: 7956 AN: 10586

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.744 AC: 50592 AN: 67974

Other (OTH) AF: 0.716 AC: 1513 AN: 2112

Alfa AF: 0.712 Hom.: 7400

Bravo AF: 0.695

Asia WGS AF: 0.768 AC: 2669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.3
DANN	Benign	0.96
PhyloP100		0.0070
PromoterAI		0.016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9333287; hg19: chr2-187455278;