Genetic Variant MAST2:p.Ser106Phe (chr1-45824572-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015112.3(MAST2):c.317C>T(p.Ser106Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000941 in 1,594,012 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000090 ( 0 hom. )

Consequence

MAST2
NM_015112.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.55

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.317C>T	p.Ser106Phe	missense	Exon 2 of 29	NP_055927.2	Q6P0Q8-1
MAST2	NM_001324320.2		c.317C>T	p.Ser106Phe	missense	Exon 2 of 30	NP_001311249.1
MAST2	NM_001319245.2		c.317C>T	p.Ser106Phe	missense	Exon 2 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.317C>T	p.Ser106Phe	missense	Exon 2 of 29	ENSP00000354671.2	Q6P0Q8-1
MAST2	ENST00000904602.1		c.317C>T	p.Ser106Phe	missense	Exon 2 of 30	ENSP00000574661.1
MAST2	ENST00000904601.1		c.317C>T	p.Ser106Phe	missense	Exon 2 of 30	ENSP00000574660.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000413

AC:

AN:

241922

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000898

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000902

AC:

AN:

1441800

Hom.:

Cov.:

AF XY:

0.00000699

AC XY:

AN XY:

715032

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32918

American (AMR)

AF:

0.00

AC:

AN:

42686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25674

East Asian (EAS)

AF:

0.00

AC:

AN:

39200

South Asian (SAS)

AF:

0.00

AC:

AN:

83324

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53080

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.0000109

AC:

AN:

1099710

Other (OTH)

AF:

0.0000168

AC:

AN:

59520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

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

AF:

0.0000131

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68050

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000828

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.035

MetaRNN

Uncertain

0.57

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.5

PhyloP100

2.6

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.3

REVEL

Benign

0.075

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0070

Polyphen

0.95

Vest4

0.60

MutPred

0.28

Loss of disorder (P = 0.0067)

MVP

0.82

MPC

0.61

ClinPred

0.66

GERP RS

5.4

Varity_R

0.24

gMVP

0.30

Mutation Taster

=86/14

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over