2-186654611-G-T

Position:

• chr2-186654611-G-T

Variant summary

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

The NM_002210.5(ITGAV):​c.1506-39G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 1,041,908 control chromosomes in the GnomAD database, including 35,667 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.20 (3932 hom., cov: 32)
  • Exomes 𝑓: 0.26 (31735 hom.)
• Consequence: ITGAV NM_002210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.803

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: This place is a probable branch point but likely benign (scored 0 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGAV	NM_002210.5	c.1506-39G>T		intron_variant		ENST00000261023.8	NP_002201.2
ITGAV	NM_001144999.3	c.1368-39G>T		intron_variant			NP_001138471.2
ITGAV	NM_001145000.3	c.1398-39G>T		intron_variant			NP_001138472.2
ITGAV	XM_047444225.1	c.663-39G>T		intron_variant			XP_047300181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGAV	ENST00000261023.8	c.1506-39G>T		intron_variant		1	NM_002210.5	ENSP00000261023	P2
	ENST00000453665.1	n.219+5883C>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.204 AC: 30980 AN: 151968 Hom.: 3932 Cov.: 32

Gnomad AFR AF: 0.0501

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.0409

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.223

GnomAD3 exomes AF: 0.232 AC: 48818 AN: 210676 Hom.: 6304 AF XY: 0.239 AC XY: 27232 AN XY: 114158

Gnomad AFR exome AF: 0.0422

Gnomad AMR exome AF: 0.247

Gnomad ASJ exome AF: 0.279

Gnomad EAS exome AF: 0.0357

Gnomad SAS exome AF: 0.246

Gnomad FIN exome AF: 0.239

Gnomad NFE exome AF: 0.278

Gnomad OTH exome AF: 0.256

GnomAD4 exome AF: 0.258 AC: 229981 AN: 889822 Hom.: 31735 Cov.: 12 AF XY: 0.260 AC XY: 120608 AN XY: 464342

Gnomad4 AFR exome AF: 0.0438

Gnomad4 AMR exome AF: 0.244

Gnomad4 ASJ exome AF: 0.282

Gnomad4 EAS exome AF: 0.0390

Gnomad4 SAS exome AF: 0.248

Gnomad4 FIN exome AF: 0.244

Gnomad4 NFE exome AF: 0.282

Gnomad4 OTH exome AF: 0.246

GnomAD4 genome AF: 0.204 AC: 30976 AN: 152086 Hom.: 3932 Cov.: 32 AF XY: 0.202 AC XY: 15020 AN XY: 74332

Gnomad4 AFR AF: 0.0500

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.0410

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.223

Alfa AF: 0.244 Hom.: 1497

Bravo AF: 0.195

Asia WGS AF: 0.135 AC: 469 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.8
DANN	Benign	0.62
BranchPoint Hunter		0.0

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: rs9333290; hg19: chr2-187519338; COSMIC: COSV53713772;