chr1-45804037-C-G

Variant names:

• chr1-45804037-C-G
• rs1020485123
• NM_015112.3:c.142C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015112.3(MAST2):​c.142C>G​(p.Arg48Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000271 in 1,106,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). 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: 0.0000027 (0 hom.)
• Consequence: MAST2 NM_015112.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.430
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36107033).

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.142C>G	p.Arg48Gly	missense	Exon 1 of 29	NP_055927.2	Q6P0Q8-1
	MAST2	NM_001324320.2		c.142C>G	p.Arg48Gly	missense	Exon 1 of 30	NP_001311249.1
	MAST2	NM_001319245.2		c.142C>G	p.Arg48Gly	missense	Exon 1 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.142C>G	p.Arg48Gly	missense	Exon 1 of 29	ENSP00000354671.2	Q6P0Q8-1
	MAST2	ENST00000904602.1		c.142C>G	p.Arg48Gly	missense	Exon 1 of 30	ENSP00000574661.1
	MAST2	ENST00000904601.1		c.142C>G	p.Arg48Gly	missense	Exon 1 of 30	ENSP00000574660.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000271 AC: 3 AN: 1106220 Hom.: 0 Cov.: 21 AF XY: 0.00000189 AC XY: 1 AN XY: 528506

African (AFR) AF: 0.00 AC: 0 AN: 22604

American (AMR) AF: 0.00 AC: 0 AN: 8368

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14814

East Asian (EAS) AF: 0.00 AC: 0 AN: 26398

South Asian (SAS) AF: 0.00 AC: 0 AN: 31554

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2940

European-Non Finnish (NFE) AF: 0.00000327 AC: 3 AN: 918710

Other (OTH) AF: 0.00 AC: 0 AN: 44282

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0063	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.052
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.65	T
M_CAP	Pathogenic	0.63	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.43
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.17
Sift	Benign	0.12	T
Sift4G	Benign	0.088	T
Polyphen		0.98	D
Vest4		0.25
MutPred		0.25		Gain of relative solvent accessibility (P = 0.0249)
MVP		0.76
MPC		0.36
ClinPred		0.69	D
GERP RS		2.8
PromoterAI		0.0060	Neutral
Varity_R		0.15
gMVP		0.16
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1020485123; hg19: chr1-46269709;