rs1430725633

Variant names:

• chr2-186602143-A-G
• rs1430725633
• NM_002210.5:c.308A>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002210.5(ITGAV):​c.308A>G​(p.Asp103Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITGAV NM_002210.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.05
• Publications: 0 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.799

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.308A>G	p.Asp103Gly	missense	Exon 2 of 30	NP_002201.2	P06756-1
	ITGAV	NM_001145000.3		c.308A>G	p.Asp103Gly	missense	Exon 2 of 28	NP_001138472.2	P06756-2
	ITGAV	NM_001144999.3		c.170A>G	p.Asp57Gly	missense	Exon 2 of 30	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.308A>G	p.Asp103Gly	missense	Exon 2 of 30	ENSP00000261023.3	P06756-1
	ITGAV	ENST00000374907.7	TSL:1	c.308A>G	p.Asp103Gly	missense	Exon 2 of 28	ENSP00000364042.3	P06756-2
	ITGAV	ENST00000925193.1		c.308A>G	p.Asp103Gly	missense	Exon 2 of 30	ENSP00000595252.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.82	D
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.056	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.47	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		6.1
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.84	P
Vest4		0.82
MutPred		0.42		Gain of catalytic residue at P99 (P = 0.0838)
MVP		0.66
MPC		0.49
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.88
gMVP		0.90
Mutation Taster		=65/35	polymorphism

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: rs1430725633; hg19: chr2-187466870;