Genetic Variant MAST2:p.Arg48Trp (chr1-45804037-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_015112.3(MAST2):c.142C>T(p.Arg48Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign 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. R48L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MAST2
NM_015112.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.430

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40967575).

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.142C>T	p.Arg48Trp	missense	Exon 1 of 29	NP_055927.2	Q6P0Q8-1
MAST2	NM_001324320.2		c.142C>T	p.Arg48Trp	missense	Exon 1 of 30	NP_001311249.1
MAST2	NM_001319245.2		c.142C>T	p.Arg48Trp	missense	Exon 1 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.142C>T	p.Arg48Trp	missense	Exon 1 of 29	ENSP00000354671.2	Q6P0Q8-1
MAST2	ENST00000904602.1		c.142C>T	p.Arg48Trp	missense	Exon 1 of 30	ENSP00000574661.1
MAST2	ENST00000904601.1		c.142C>T	p.Arg48Trp	missense	Exon 1 of 30	ENSP00000574660.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1106220

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

528506

African (AFR)

AF:

0.00

AC:

AN:

22604

American (AMR)

AF:

0.00

AC:

AN:

8368

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14814

East Asian (EAS)

AF:

0.00

AC:

AN:

26398

South Asian (SAS)

AF:

0.00

AC:

AN:

31554

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36550

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2940

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

918710

Other (OTH)

AF:

0.00

AC:

AN:

44282

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Uncertain

0.093

BayesDel_noAF

Benign

-0.10

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0066

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.11

FATHMM_MKL

Benign

0.36

LIST_S2

Benign

0.79

M_CAP

Pathogenic

0.70

MetaRNN

Benign

0.41

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.4

PhyloP100

0.43

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-1.0

REVEL

Benign

0.17

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.019

Polyphen

1.0

Vest4

0.15

MutPred

0.26

Gain of catalytic residue at P51 (P = 0.0333)

MVP

0.82

MPC

0.44

ClinPred

0.90

GERP RS

2.8

PromoterAI

-0.0023

Neutral

(source)

Varity_R

0.17

gMVP

0.12

Mutation Taster

=86/14

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over