NM_002203.4:c.1944-183A>T

Variant names:

• chr5-53066935-A-T
• rs3212556
• NM_002203.4:c.1944-183A>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002203.4(ITGA2):​c.1944-183A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 150,428 control chromosomes in the GnomAD database, including 3,301 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (3301 hom., cov: 32)
• Consequence: ITGA2 NM_002203.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.522
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 5-53066935-A-T is Benign according to our data. Variant chr5-53066935-A-T is described in ClinVar as Benign. ClinVar VariationId is 1277623.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	NM_002203.4	MANE Select	c.1944-183A>T		intron	N/A	NP_002194.2
	ITGA2	NR_073103.2		n.2061-183A>T		intron	N/A
	ITGA2	NR_073104.2		n.2061-183A>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	ENST00000296585.10	TSL:1 MANE Select	c.1944-183A>T		intron	N/A	ENSP00000296585.5
	ITGA2	ENST00000509814.5	TSL:1	n.1944-183A>T		intron	N/A	ENSP00000424397.1
	ITGA2	ENST00000509960.5	TSL:1	n.*59-183A>T		intron	N/A	ENSP00000424642.1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29408 AN: 150316 Hom.: 3294 Cov.: 32

Gnomad AFR AF: 0.0692

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.202

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.201

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.196 AC: 29432 AN: 150428 Hom.: 3301 Cov.: 32 AF XY: 0.200 AC XY: 14664 AN XY: 73384

African (AFR) AF: 0.0691 AC: 2838 AN: 41046

American (AMR) AF: 0.228 AC: 3435 AN: 15060

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 834 AN: 3454

East Asian (EAS) AF: 0.195 AC: 996 AN: 5100

South Asian (SAS) AF: 0.278 AC: 1322 AN: 4754

European-Finnish (FIN) AF: 0.284 AC: 2936 AN: 10336

Middle Eastern (MID) AF: 0.219 AC: 63 AN: 288

European-Non Finnish (NFE) AF: 0.243 AC: 16366 AN: 67386

Other (OTH) AF: 0.200 AC: 419 AN: 2094

Alfa AF: 0.205 Hom.: 483

Bravo AF: 0.181

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.23
DANN	Benign	0.088
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism (auto)

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: rs3212556; hg19: chr5-52362765; COSMIC: COSV56857265;