rs762258496

Variant names:

• chr1-45824454-C-A
• rs762258496
• NM_015112.3:c.199C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-45824454-C-A
• chr1-45824454-C-G
• chr1-45824454-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015112.3(MAST2):​c.199C>A​(p.Pro67Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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. P67S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAST2 NM_015112.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.85
• Publications: 0 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2510671).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAST2	NM_015112.3	MANE Select	c.199C>A	p.Pro67Thr	missense	Exon 2 of 29	NP_055927.2	Q6P0Q8-1
	MAST2	NM_001324320.2		c.199C>A	p.Pro67Thr	missense	Exon 2 of 30	NP_001311249.1
	MAST2	NM_001319245.2		c.199C>A	p.Pro67Thr	missense	Exon 2 of 29	NP_001306174.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAST2	ENST00000361297.7	TSL:1 MANE Select	c.199C>A	p.Pro67Thr	missense	Exon 2 of 29	ENSP00000354671.2	Q6P0Q8-1
	MAST2	ENST00000904602.1		c.199C>A	p.Pro67Thr	missense	Exon 2 of 30	ENSP00000574661.1
	MAST2	ENST00000904601.1		c.199C>A	p.Pro67Thr	missense	Exon 2 of 30	ENSP00000574660.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	1.9	L
PhyloP100		3.9
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.10
Sift	Uncertain	0.027	D
Sift4G	Benign	0.18	T
Polyphen		0.64	P
Vest4		0.44
MutPred		0.33		Loss of disorder (P = 0.1158)
MVP		0.83
MPC		0.89
ClinPred		0.92	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.13
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs762258496; hg19: chr1-46290126;