2-186668641-C-T

Variant names:

• chr2-186668641-C-T
• rs11685758
• NM_002210.5:c.2434-121C>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.2434-121C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 775,598 control chromosomes in the GnomAD database, including 33,466 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 0.27 (5704 hom., cov: 30)
  • Exomes 𝑓: 0.29 (27762 hom.)
• Consequence: ITGAV NM_002210.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.597
• Publications: 11 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:41242):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.363 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002210.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAV	NM_002210.5	MANE Select	c.2434-121C>T		intron	N/A	NP_002201.2	P06756-1
	ITGAV	NM_001145000.3		c.2326-121C>T		intron	N/A	NP_001138472.2	P06756-2
	ITGAV	NM_001144999.3		c.2296-121C>T		intron	N/A	NP_001138471.2	P06756-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGAV	ENST00000261023.8	TSL:1 MANE Select	c.2434-121C>T		intron	N/A	ENSP00000261023.3	P06756-1
	ITGAV	ENST00000374907.7	TSL:1	c.2326-121C>T		intron	N/A	ENSP00000364042.3	P06756-2
	ITGAV	ENST00000925193.1		c.2434-121C>T		intron	N/A	ENSP00000595252.1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41096 AN: 151826 Hom.: 5703 Cov.: 30

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.285

GnomAD4 exome AF: 0.292 AC: 181800 AN: 623652 Hom.: 27762 Cov.: 8 AF XY: 0.297 AC XY: 98769 AN XY: 332566

African (AFR) AF: 0.212 AC: 3188 AN: 15018

American (AMR) AF: 0.290 AC: 6332 AN: 21808

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 5882 AN: 17690

East Asian (EAS) AF: 0.113 AC: 3712 AN: 32922

South Asian (SAS) AF: 0.379 AC: 21316 AN: 56188

European-Finnish (FIN) AF: 0.268 AC: 12992 AN: 48548

Middle Eastern (MID) AF: 0.362 AC: 1443 AN: 3990

European-Non Finnish (NFE) AF: 0.298 AC: 117719 AN: 395620

Other (OTH) AF: 0.289 AC: 9216 AN: 31868

GnomAD4 genome AF: 0.271 AC: 41122 AN: 151946 Hom.: 5704 Cov.: 30 AF XY: 0.270 AC XY: 20044 AN XY: 74218

African (AFR) AF: 0.210 AC: 8709 AN: 41458

American (AMR) AF: 0.286 AC: 4366 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1193 AN: 3468

East Asian (EAS) AF: 0.145 AC: 749 AN: 5162

South Asian (SAS) AF: 0.377 AC: 1812 AN: 4802

European-Finnish (FIN) AF: 0.257 AC: 2708 AN: 10526

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20571 AN: 67960

Other (OTH) AF: 0.286 AC: 605 AN: 2112

Alfa AF: 0.292 Hom.: 1075

Bravo AF: 0.268

Asia WGS AF: 0.268 AC: 932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.2
DANN	Benign	0.36
PhyloP100		0.60
PromoterAI		0.0045	Neutral
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11685758; hg19: chr2-187533368; COSMIC: COSV53710449; COSMIC: COSV53710449;