Genetic Variant MAST2:p.Arg188Pro (chr1-45959448-G-C) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_015112.3(MAST2):c.563G>C(p.Arg188Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R188Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MAST2
NM_015112.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.98

Publications

0 publications found

Variant links:

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

MAST2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.819

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAST2	NM_015112.3	MANE Select	c.563G>C	p.Arg188Pro	missense	Exon 5 of 29	NP_055927.2	Q6P0Q8-1
MAST2	NM_001324320.2		c.563G>C	p.Arg188Pro	missense	Exon 5 of 30	NP_001311249.1
MAST2	NM_001319245.2		c.563G>C	p.Arg188Pro	missense	Exon 5 of 29	NP_001306174.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAST2	ENST00000361297.7	TSL:1 MANE Select	c.563G>C	p.Arg188Pro	missense	Exon 5 of 29	ENSP00000354671.2	Q6P0Q8-1
MAST2	ENST00000904602.1		c.758G>C	p.Arg253Pro	missense	Exon 6 of 30	ENSP00000574661.1
MAST2	ENST00000904601.1		c.563G>C	p.Arg188Pro	missense	Exon 5 of 30	ENSP00000574660.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461442

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727016

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33448

American (AMR)

AF:

0.00

AC:

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

86228

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111754

Other (OTH)

AF:

0.00

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

M_CAP

Uncertain

0.12

MetaRNN

Pathogenic

0.82

MetaSVM

Uncertain

-0.24

MutationAssessor

Uncertain

2.4

PhyloP100

9.0

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-6.6

REVEL

Pathogenic

0.67

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.70

MutPred

0.43

Gain of glycosylation at R188 (P = 0.0053)

MVP

0.90

MPC

1.0

ClinPred

0.99

GERP RS

5.1

Varity_R

0.89

gMVP

0.62

Mutation Taster

=60/40

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over