2-186657954-A-G

Variant names:

• chr2-186657954-A-G
• rs7565633
• NM_002210.5:c.1720-1084A>G

Variant summary

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

The NM_002210.5(ITGAV):​c.1720-1084A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 107,672 control chromosomes in the GnomAD database, including 6,739 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 0.40 (6739 hom., cov: 26)
• Consequence: ITGAV NM_002210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300
• Publications: 6 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]

ENSG00000227227 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAV	NM_002210.5	c.1720-1084A>G		intron_variant	Intron 17 of 29	ENST00000261023.8	NP_002201.2
ITGAV	NM_001145000.3	c.1612-1084A>G		intron_variant	Intron 15 of 27		NP_001138472.2
ITGAV	NM_001144999.3	c.1582-1084A>G		intron_variant	Intron 17 of 29		NP_001138471.2
ITGAV	XM_047444225.1	c.877-1084A>G		intron_variant	Intron 13 of 25		XP_047300181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAV	ENST00000261023.8	c.1720-1084A>G		intron_variant	Intron 17 of 29	1	NM_002210.5	ENSP00000261023.3

Frequencies

GnomAD3 genomes AF: 0.402 AC: 43222 AN: 107588 Hom.: 6740 Cov.: 26

Gnomad AFR AF: 0.251

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.401 AC: 43222 AN: 107672 Hom.: 6739 Cov.: 26 AF XY: 0.402 AC XY: 20843 AN XY: 51898

African (AFR) AF: 0.251 AC: 7611 AN: 30362

American (AMR) AF: 0.403 AC: 3897 AN: 9660

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1219 AN: 2656

East Asian (EAS) AF: 0.423 AC: 402 AN: 950

South Asian (SAS) AF: 0.419 AC: 1536 AN: 3668

European-Finnish (FIN) AF: 0.472 AC: 3141 AN: 6648

Middle Eastern (MID) AF: 0.438 AC: 105 AN: 240

European-Non Finnish (NFE) AF: 0.474 AC: 24238 AN: 51164

Other (OTH) AF: 0.416 AC: 625 AN: 1504

Alfa AF: 0.252 Hom.: 1019

Bravo AF: 0.277

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.7
DANN	Benign	0.79
PhyloP100		0.0030
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: rs7565633; hg19: chr2-187522681;