5-52989502-C-T

Variant names:

• chr5-52989502-C-T
• rs758607230
• NM_002203.4:c.34C>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>T​(p.Pro12Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign 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. P12R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ITGA2 NM_002203.4 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.08692771).

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>T	p.Pro12Ser	missense	Exon 1 of 30	NP_002194.2	P17301
	ITGA2	NR_073103.2		n.151C>T		non_coding_transcript_exon	Exon 1 of 29
	ITGA2	NR_073104.2		n.151C>T		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>T	p.Pro12Ser	missense	Exon 1 of 30	ENSP00000296585.5	P17301
	ITGA2	ENST00000509814.5	TSL:1	n.34C>T		non_coding_transcript_exon	Exon 1 of 29	ENSP00000424397.1	E7EMF1
	ITGA2	ENST00000509960.5	TSL:1	n.34C>T		non_coding_transcript_exon	Exon 1 of 30	ENSP00000424642.1	E9PB77

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	7.8
DANN	Benign	0.92
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.040	N
M_CAP	Uncertain	0.095	D
MetaRNN	Benign	0.087	T
MetaSVM	Benign	-0.49	T
PhyloP100		0.28
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.42	N
REVEL	Benign	0.17
Sift	Benign	0.47	T
Sift4G	Benign	0.90	T
Vest4		0.15
MutPred		0.46		Loss of loop (P = 0.0073)
MVP		0.86
MPC		0.17
ClinPred		0.076	T
GERP RS		2.2
PromoterAI		-0.044	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
gMVP		0.41
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; COSMIC: COSV107370781;