5-53094196-A-AATTTATAAACAATTTTGTAGGACT

Variant names:

• chr5-53094196-A-AATTTATAAACAATTTTGTAGGACT
• rs57674800
• NM_002203.4:c.*3599_*3600insTTATAAACAATTTTGTAGGACTAT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_002203.4(ITGA2):​c.*3599_*3600insTTATAAACAATTTTGTAGGACTAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0012 (1 hom., cov: 0)
• Consequence: ITGA2 NM_002203.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.877
• Publications: 3 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 Gene-Disease associations (from GenCC):

• platelet-type bleeding disorder 9

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00118 (179/152060) while in subpopulation SAS AF = 0.0266 (128/4812). AF 95% confidence interval is 0.0229. There are 1 homozygotes in GnomAd4. There are 121 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 179 AD gene.

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.*3599_*3600insTTATAAACAATTTTGTAGGACTAT		3_prime_UTR	Exon 30 of 30	NP_002194.2	P17301
	ITGA2	NR_073103.2		n.7159_7160insTTATAAACAATTTTGTAGGACTAT		non_coding_transcript_exon	Exon 29 of 29
	ITGA2	NR_073104.2		n.7120_7121insTTATAAACAATTTTGTAGGACTAT		non_coding_transcript_exon	Exon 29 of 29

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	ENST00000296585.10	TSL:1 MANE Select	c.*3599_*3600insTTATAAACAATTTTGTAGGACTAT		3_prime_UTR	Exon 30 of 30	ENSP00000296585.5	P17301

Frequencies

GnomAD3 genomes AF: 0.00118 AC: 180 AN: 151944 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00848

Gnomad SAS AF: 0.0268

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000956

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.00118 AC: 179 AN: 152060 Hom.: 1 Cov.: 0 AF XY: 0.00163 AC XY: 121 AN XY: 74306

African (AFR) AF: 0.0000723 AC: 3 AN: 41486

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00850 AC: 44 AN: 5176

South Asian (SAS) AF: 0.0266 AC: 128 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67948

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00 Hom.: 341

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.88
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs57674800; hg19: chr5-52390026;