Genetic Variant MAST2:p.Ala52Ser (chr1-45804049-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015112.3(MAST2):c.154G>T(p.Ala52Ser) 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. 16/22 in silico tools predict 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. A52P) 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: -0.920

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029301703).

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.154G>T	p.Ala52Ser	missense	Exon 1 of 29	NP_055927.2	Q6P0Q8-1
MAST2	NM_001324320.2		c.154G>T	p.Ala52Ser	missense	Exon 1 of 30	NP_001311249.1
MAST2	NM_001319245.2		c.154G>T	p.Ala52Ser	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.154G>T	p.Ala52Ser	missense	Exon 1 of 29	ENSP00000354671.2	Q6P0Q8-1
MAST2	ENST00000904602.1		c.154G>T	p.Ala52Ser	missense	Exon 1 of 30	ENSP00000574661.1
MAST2	ENST00000904601.1		c.154G>T	p.Ala52Ser	missense	Exon 1 of 30	ENSP00000574660.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1033800

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

494308

African (AFR)

AF:

0.00

AC:

AN:

20216

American (AMR)

AF:

0.00

AC:

AN:

6804

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12106

East Asian (EAS)

AF:

0.00

AC:

AN:

22612

South Asian (SAS)

AF:

0.00

AC:

AN:

30284

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31806

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2596

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

867592

Other (OTH)

AF:

0.00

AC:

AN:

39784

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.68

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.0071

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.28

M_CAP

Benign

0.085

MetaRNN

Benign

0.029

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.92

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.020

REVEL

Benign

0.048

Sift

Benign

0.39

Sift4G

Benign

0.20

Polyphen

0.0

Vest4

0.038

MutPred

0.23

Gain of phosphorylation at A52 (P = 0.0146)

MVP

0.35

MPC

0.20

ClinPred

0.057

GERP RS

-5.6

PromoterAI

-0.039

Neutral

(source)

Varity_R

0.040

gMVP

0.050

Mutation Taster

=94/6

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

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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