1-45997209-A-G

Variant names:

• chr1-45997209-A-G
• rs4073846
• NM_015112.3:c.593-515A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015112.3(MAST2):​c.593-515A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 152,020 control chromosomes in the GnomAD database, including 15,338 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.45 (15338 hom., cov: 32)
• Consequence: MAST2 NM_015112.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• Publications: 15 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

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.593-515A>G		intron	N/A	NP_055927.2	Q6P0Q8-1
	MAST2	NM_001324320.2		c.593-515A>G		intron	N/A	NP_001311249.1
	MAST2	NM_001319245.2		c.593-515A>G		intron	N/A	NP_001306174.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAST2	ENST00000361297.7	TSL:1 MANE Select	c.593-515A>G		intron	N/A	ENSP00000354671.2	Q6P0Q8-1
	MAST2	ENST00000904602.1		c.788-515A>G		intron	N/A	ENSP00000574661.1
	MAST2	ENST00000904601.1		c.593-515A>G		intron	N/A	ENSP00000574660.1

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67878 AN: 151902 Hom.: 15353 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.441

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.446 AC: 67858 AN: 152020 Hom.: 15338 Cov.: 32 AF XY: 0.447 AC XY: 33206 AN XY: 74304

African (AFR) AF: 0.421 AC: 17469 AN: 41450

American (AMR) AF: 0.488 AC: 7457 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1623 AN: 3468

East Asian (EAS) AF: 0.629 AC: 3257 AN: 5178

South Asian (SAS) AF: 0.447 AC: 2152 AN: 4816

European-Finnish (FIN) AF: 0.413 AC: 4362 AN: 10570

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30084 AN: 67952

Other (OTH) AF: 0.435 AC: 918 AN: 2110

Alfa AF: 0.424 Hom.: 7504

Bravo AF: 0.451

Asia WGS AF: 0.523 AC: 1816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.052
DANN	Benign	0.40
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4073846; hg19: chr1-46462881; COSMIC: COSV63617106;