rs754337745

Variant names:

• chr2-186602098-A-C
• rs754337745
• NM_002210.5:c.263A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-186602098-A-C
• chr2-186602098-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BS2

The NM_002210.5(ITGAV):​c.263A>C​(p.Lys88Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,360 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. K88R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ITGAV NM_002210.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGAV	NM_002210.5	c.263A>C	p.Lys88Thr	missense_variant	Exon 2 of 30	ENST00000261023.8	NP_002201.2
ITGAV	NM_001145000.3	c.263A>C	p.Lys88Thr	missense_variant	Exon 2 of 28		NP_001138472.2
ITGAV	NM_001144999.3	c.125A>C	p.Lys42Thr	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.263A>C	p.Lys88Thr	missense_variant	Exon 2 of 30	1	NM_002210.5	ENSP00000261023.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461360 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726984

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111688

Other (OTH) AF: 0.0000166 AC: 1 AN: 60362

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T;.;.
Eigen	Benign	0.045
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Uncertain	0.88	D;T;T
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Uncertain	2.7	M;M;.
PhyloP100		1.5
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.67	N;N;N
REVEL	Uncertain	0.52
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.28	T;T;T
Polyphen		0.34	B;B;.
Vest4		0.69
MutPred		0.52		Loss of methylation at K88 (P = 0.0091);Loss of methylation at K88 (P = 0.0091);.;
MVP		0.76
MPC		0.31
ClinPred		0.75	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.50
gMVP		0.58
Mutation Taster		=58/42	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: rs754337745; hg19: chr2-187466825;