rs10890361

Variant names:

• chr1-45880562-T-A
• rs10890361
• NM_015112.3:c.469-1802T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015112.3(MAST2):​c.469-1802T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 152,044 control chromosomes in the GnomAD database, including 15,276 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (15276 hom., cov: 32)
• Consequence: MAST2 NM_015112.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.443
• Publications: 8 publications found

Genes affected

MAST2 (HGNC:19035): (microtubule associated serine/threonine kinase 2) Enables phosphatase binding activity. Predicted to be involved in several processes, including peptidyl-serine phosphorylation; regulation of interleukin-12 production; and spermatid differentiation. Predicted to be located in cytoplasm and plasma membrane. Predicted to be active in microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

MAST2 Gene-Disease associations (from GenCC):

• thrombotic disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

LOC105378694 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015112.3. 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
	MAST2	NM_015112.3	MANE Select	c.469-1802T>A		intron	N/A	NP_055927.2	Q6P0Q8-1
	MAST2	NM_001324320.2		c.469-1802T>A		intron	N/A	NP_001311249.1
	MAST2	NM_001319245.2		c.469-1802T>A		intron	N/A	NP_001306174.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAST2	ENST00000361297.7	TSL:1 MANE Select	c.469-1802T>A		intron	N/A	ENSP00000354671.2	Q6P0Q8-1
	MAST2	ENST00000904602.1		c.469-1802T>A		intron	N/A	ENSP00000574661.1
	MAST2	ENST00000904601.1		c.469-1802T>A		intron	N/A	ENSP00000574660.1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67719 AN: 151924 Hom.: 15291 Cov.: 32

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.381

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.441

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

GnomAD4 genome AF: 0.445 AC: 67699 AN: 152044 Hom.: 15276 Cov.: 32 AF XY: 0.446 AC XY: 33148 AN XY: 74312

African (AFR) AF: 0.419 AC: 17364 AN: 41464

American (AMR) AF: 0.490 AC: 7476 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1620 AN: 3468

East Asian (EAS) AF: 0.620 AC: 3210 AN: 5178

South Asian (SAS) AF: 0.446 AC: 2152 AN: 4820

European-Finnish (FIN) AF: 0.413 AC: 4362 AN: 10554

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.442 AC: 30060 AN: 67974

Other (OTH) AF: 0.435 AC: 919 AN: 2112

Alfa AF: 0.441 Hom.: 1840

Bravo AF: 0.449

Asia WGS AF: 0.518 AC: 1797 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.5
DANN	Benign	0.80
PhyloP100		0.44
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: rs10890361; hg19: chr1-46346234; COSMIC: COSV63616938;