rs79932422

Positions:

• chr5-53073171-C-A
• chr5-53073171-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002203.4(ITGA2):​c.2483C>A​(p.Thr828Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: ITGA2 NM_002203.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193

Genes affected

ITGA2 (HGNC:6137): (integrin subunit alpha 2) This gene encodes the alpha subunit of a transmembrane receptor for collagens and related proteins. The encoded protein forms a heterodimer with a beta subunit and mediates the adhesion of platelets and other cell types to the extracellular matrix. Loss of the encoded protein is associated with bleeding disorder platelet-type 9. Antibodies against this protein are found in several immune disorders, including neonatal alloimmune thrombocytopenia. This gene is located adjacent to a related alpha subunit gene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

ITGA2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18987614).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGA2	NM_002203.4	c.2483C>A	p.Thr828Lys	missense_variant	20/30	ENST00000296585.10	NP_002194.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGA2	ENST00000296585.10	c.2483C>A	p.Thr828Lys	missense_variant	20/30	1	NM_002203.4	ENSP00000296585.5

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151830 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151830 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74118

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	6.8
DANN	Benign	0.91
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.082	N
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.056
Sift	Benign	0.12	T
Sift4G	Benign	0.34	T
Vest4		0.17
MutPred		0.62		Gain of MoRF binding (P = 0.0301);
MVP		0.79
MPC		0.21
ClinPred		0.13	T
GERP RS		-0.45
gMVP		0.41

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: rs79932422; hg19: chr5-52369001;