rs1801106

Variant names:

• chr5-53062927-G-A
• rs1801106
• NM_002203.4:c.1600G>A
• ITGA2 p.Glu534Lys

Your query was ambiguous. Multiple possible variants found:

• chr5-53062927-G-A
• chr5-53062927-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002203.4(ITGA2):​c.1600G>A​(p.Glu534Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0901 in 1,598,154 control chromosomes in the GnomAD database, including 7,290 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1140 hom., cov: 32)
  • Exomes 𝑓: 0.088 (6150 hom.)
• Consequence: ITGA2 NM_002203.4 missense, splice_region
• Scores: Splicing: ADA: 0.00001115
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.00
• Publications: 28 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0011746883).
• BP6: Variant 5-53062927-G-A is Benign according to our data. Variant chr5-53062927-G-A is described in ClinVar as Benign. ClinVar VariationId is 353753.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	NM_002203.4	MANE Select	c.1600G>A	p.Glu534Lys	missense splice_region	Exon 13 of 30	NP_002194.2	P17301
	ITGA2	NR_073103.2		n.1717G>A		splice_region non_coding_transcript_exon	Exon 13 of 29
	ITGA2	NR_073104.2		n.1717G>A		splice_region non_coding_transcript_exon	Exon 13 of 29

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITGA2	ENST00000296585.10	TSL:1 MANE Select	c.1600G>A	p.Glu534Lys	missense splice_region	Exon 13 of 30	ENSP00000296585.5	P17301
	ITGA2	ENST00000509814.5	TSL:1	n.1600G>A		splice_region non_coding_transcript_exon	Exon 13 of 29	ENSP00000424397.1	E7EMF1
	ITGA2	ENST00000509960.5	TSL:1	n.1600G>A		splice_region non_coding_transcript_exon	Exon 13 of 30	ENSP00000424642.1	E9PB77

Frequencies

GnomAD3 genomes AF: 0.113 AC: 16833 AN: 149358 Hom.: 1132 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.0385

Gnomad AMR AF: 0.0850

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0269

Gnomad SAS AF: 0.0873

Gnomad FIN AF: 0.0587

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.0903

Gnomad OTH AF: 0.124

GnomAD2 exomes AF: 0.0856 AC: 20898 AN: 244036 AF XY: 0.0867

Gnomad AFR exome AF: 0.190

Gnomad AMR exome AF: 0.0597

Gnomad ASJ exome AF: 0.114

Gnomad EAS exome AF: 0.0193

Gnomad FIN exome AF: 0.0540

Gnomad NFE exome AF: 0.0914

Gnomad OTH exome AF: 0.0961

GnomAD4 exome AF: 0.0877 AC: 127055 AN: 1448680 Hom.: 6150 Cov.: 31 AF XY: 0.0883 AC XY: 63645 AN XY: 720734

African (AFR) AF: 0.193 AC: 6340 AN: 32862

American (AMR) AF: 0.0621 AC: 2712 AN: 43658

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 2968 AN: 25796

East Asian (EAS) AF: 0.0338 AC: 1330 AN: 39324

South Asian (SAS) AF: 0.0896 AC: 7600 AN: 84826

European-Finnish (FIN) AF: 0.0531 AC: 2814 AN: 52982

Middle Eastern (MID) AF: 0.153 AC: 870 AN: 5680

European-Non Finnish (NFE) AF: 0.0876 AC: 96716 AN: 1103902

Other (OTH) AF: 0.0956 AC: 5705 AN: 59650

GnomAD4 genome AF: 0.113 AC: 16880 AN: 149474 Hom.: 1140 Cov.: 32 AF XY: 0.109 AC XY: 7943 AN XY: 72770

African (AFR) AF: 0.188 AC: 7670 AN: 40796

American (AMR) AF: 0.0849 AC: 1277 AN: 15046

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 386 AN: 3448

East Asian (EAS) AF: 0.0269 AC: 136 AN: 5048

South Asian (SAS) AF: 0.0873 AC: 415 AN: 4756

European-Finnish (FIN) AF: 0.0587 AC: 576 AN: 9820

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.0903 AC: 6077 AN: 67290

Other (OTH) AF: 0.125 AC: 259 AN: 2068

Alfa AF: 0.0938 Hom.: 2661

Bravo AF: 0.117

Asia WGS AF: 0.0890 AC: 308 AN: 3470

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Platelet-type bleeding disorder 9 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.83
Eigen	Benign	0.00062
Eigen_PC	Benign	0.025
FATHMM_MKL	Benign	0.38	N
MetaRNN	Benign	0.0012	T
MetaSVM	Benign	-0.94	T
PhyloP100		3.0
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.59	N
REVEL	Benign	0.057
Sift	Benign	0.88	T
Sift4G	Benign	1.0	T
gMVP		0.54
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000011
dbscSNV1_RF	Benign	0.0
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1801106;

hg19: chr5-52358757;