chr1-45997739-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_015112.3(MAST2):ā€‹c.608A>Gā€‹(p.Asp203Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.000021 ( 0 hom. )

Consequence

MAST2
NM_015112.3 missense

Scores

8
5
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.95
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.788

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MAST2NM_015112.3 linkuse as main transcriptc.608A>G p.Asp203Gly missense_variant 6/29 ENST00000361297.7 NP_055927.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MAST2ENST00000361297.7 linkuse as main transcriptc.608A>G p.Asp203Gly missense_variant 6/291 NM_015112.3 ENSP00000354671 Q6P0Q8-1
MAST2ENST00000674079.1 linkuse as main transcriptc.158A>G p.Asp53Gly missense_variant 3/27 ENSP00000501318 P1
MAST2ENST00000372008.6 linkuse as main transcriptc.263A>G p.Asp88Gly missense_variant 4/205 ENSP00000361078
MAST2ENST00000482881.1 linkuse as main transcriptn.108A>G non_coding_transcript_exon_variant 2/63

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152184
Hom.:
0
Cov.:
32
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
GnomAD3 exomes
AF:
0.00000801
AC:
2
AN:
249544
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135384
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000205
AC:
30
AN:
1461808
Hom.:
0
Cov.:
30
AF XY:
0.0000220
AC XY:
16
AN XY:
727210
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000261
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152184
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000533
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.00000828
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 20, 2023The c.608A>G (p.D203G) alteration is located in exon 6 (coding exon 6) of the MAST2 gene. This alteration results from a A to G substitution at nucleotide position 608, causing the aspartic acid (D) at amino acid position 203 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.91
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.16
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
T;.
Eigen
Pathogenic
0.76
Eigen_PC
Pathogenic
0.77
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.93
D;D
M_CAP
Benign
0.033
D
MetaRNN
Pathogenic
0.79
D;D
MetaSVM
Benign
-0.72
T
MutationAssessor
Uncertain
2.2
M;.
MutationTaster
Benign
1.0
D;D;N
PrimateAI
Uncertain
0.71
T
PROVEAN
Pathogenic
-6.6
D;D
REVEL
Uncertain
0.51
Sift
Benign
0.039
D;T
Sift4G
Benign
0.10
T;T
Polyphen
0.74
P;.
Vest4
0.61
MVP
0.79
MPC
0.97
ClinPred
0.98
D
GERP RS
5.8
Varity_R
0.59
gMVP
0.53

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs774377481; hg19: chr1-46463411; API