rs2105655315

Variant names:

• chr2-186602059-C-A
• rs2105655315
• NM_002210.5:c.224C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-186602059-C-A
• chr2-186602059-C-G
• chr2-186602059-C-T

Variant summary

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

The NM_002210.5(ITGAV):​c.224C>A​(p.Thr75Asn) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T75I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ITGAV NM_002210.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.11
• 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, 0.801

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAV	NM_002210.5	c.224C>A	p.Thr75Asn	missense_variant	Exon 2 of 30	ENST00000261023.8	NP_002201.2
ITGAV	NM_001145000.3	c.224C>A	p.Thr75Asn	missense_variant	Exon 2 of 28		NP_001138472.2
ITGAV	NM_001144999.3	c.86C>A	p.Thr29Asn	missense_variant	Exon 2 of 30		NP_001138471.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGAV	ENST00000261023.8	c.224C>A	p.Thr75Asn	missense_variant	Exon 2 of 30	1	NM_002210.5	ENSP00000261023.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.78	D;.;.
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.86	D;D;D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.80	D;D;D
MetaSVM	Pathogenic	0.88	D
MutationAssessor	Uncertain	2.1	M;M;.
PhyloP100		5.1
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.7	D;D;D
REVEL	Uncertain	0.50
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.67
MutPred		0.33		Loss of glycosylation at T75 (P = 0.0596);Loss of glycosylation at T75 (P = 0.0596);.;
MVP		0.99
MPC		0.78
ClinPred		0.99	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.85
gMVP		0.84
Mutation Taster		=76/24	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: rs2105655315; hg19: chr2-187466786;