rs758607230

Variant names:

• chr5-52989502-C-A
• rs758607230
• NM_002203.4:c.34C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-52989502-C-A
• chr5-52989502-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002203.4(ITGA2):​c.34C>A​(p.Pro12Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P12R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ITGA2 NM_002203.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.280
• Publications: 0 publications found

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-AS1 (HGNC:40306): (ITGA2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07887331).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002203.4. 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
	ITGA2	NM_002203.4	MANE Select	c.34C>A	p.Pro12Thr	missense	Exon 1 of 30	NP_002194.2	P17301
	ITGA2	NR_073103.2		n.151C>A		non_coding_transcript_exon	Exon 1 of 29
	ITGA2	NR_073104.2		n.151C>A		non_coding_transcript_exon	Exon 1 of 29

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	ENST00000296585.10	TSL:1 MANE Select	c.34C>A	p.Pro12Thr	missense	Exon 1 of 30	ENSP00000296585.5	P17301
	ITGA2	ENST00000509814.5	TSL:1	n.34C>A		non_coding_transcript_exon	Exon 1 of 29	ENSP00000424397.1	E7EMF1
	ITGA2	ENST00000509960.5	TSL:1	n.34C>A		non_coding_transcript_exon	Exon 1 of 30	ENSP00000424642.1	E9PB77

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000796 AC: 2 AN: 251234 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461812 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727216

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111956

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	7.3
DANN	Benign	0.86
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.056	N
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.079	T
MetaSVM	Benign	-0.42	T
PhyloP100		0.28
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.68	N
REVEL	Benign	0.19
Sift	Benign	0.68	T
Sift4G	Benign	0.77	T
Vest4		0.17
MutPred		0.47		Loss of loop (P = 0.0073)
MVP		0.87
MPC		0.19
ClinPred		0.035	T
GERP RS		2.2
PromoterAI		0.036	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
gMVP		0.46
Mutation Taster		=92/8	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: rs758607230; hg19: chr5-52285332;