2-186628237-A-G

Variant names:

• chr2-186628237-A-G
• rs13006571
• NM_002210.5:c.524-2560A>G

Variant summary

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

The NM_002210.5(ITGAV):​c.524-2560A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 152,040 control chromosomes in the GnomAD database, including 40,560 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 0.73 (40560 hom., cov: 33)
• Consequence: ITGAV NM_002210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAV	NM_002210.5	c.524-2560A>G		intron_variant	Intron 4 of 29	ENST00000261023.8	NP_002201.2
ITGAV	NM_001145000.3	c.523+2650A>G		intron_variant	Intron 4 of 27		NP_001138472.2
ITGAV	NM_001144999.3	c.386-2560A>G		intron_variant	Intron 4 of 29		NP_001138471.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAV	ENST00000261023.8	c.524-2560A>G		intron_variant	Intron 4 of 29	1	NM_002210.5	ENSP00000261023.3

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110939 AN: 151922 Hom.: 40532 Cov.: 33

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.814

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.750

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.742

Gnomad OTH AF: 0.737

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

GnomAD4 genome AF: 0.730 AC: 111024 AN: 152040 Hom.: 40560 Cov.: 33 AF XY: 0.730 AC XY: 54265 AN XY: 74328

Gnomad4 AFR AF: 0.690

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.713

Gnomad4 EAS AF: 0.852

Gnomad4 SAS AF: 0.741

Gnomad4 FIN AF: 0.750

Gnomad4 NFE AF: 0.742

Gnomad4 OTH AF: 0.735

Alfa AF: 0.723 Hom.: 6708

Bravo AF: 0.727

Asia WGS AF: 0.776 AC: 2699 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.1
DANN	Benign	0.39

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: rs13006571; hg19: chr2-187492964;