rs1644065016

Variant names:

• chr1-45804049-G-C
• rs1644065016
• NM_015112.3:c.154G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-45804049-G-C
• chr1-45804049-G-A
• chr1-45804049-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015112.3(MAST2):​c.154G>C​(p.Ala52Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.00013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAST2 NM_015112.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.920
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046587616).

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.154G>C	p.Ala52Pro	missense	Exon 1 of 29	NP_055927.2	Q6P0Q8-1
	MAST2	NM_001324320.2		c.154G>C	p.Ala52Pro	missense	Exon 1 of 30	NP_001311249.1
	MAST2	NM_001319245.2		c.154G>C	p.Ala52Pro	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.154G>C	p.Ala52Pro	missense	Exon 1 of 29	ENSP00000354671.2	Q6P0Q8-1
	MAST2	ENST00000904602.1		c.154G>C	p.Ala52Pro	missense	Exon 1 of 30	ENSP00000574661.1
	MAST2	ENST00000904601.1		c.154G>C	p.Ala52Pro	missense	Exon 1 of 30	ENSP00000574660.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000132 AC: 136 AN: 1033500 Hom.: 0 Cov.: 27 AF XY: 0.000132 AC XY: 65 AN XY: 494154

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000495 AC: 10 AN: 20204

American (AMR) AF: 0.000736 AC: 5 AN: 6798

Ashkenazi Jewish (ASJ) AF: 0.000662 AC: 8 AN: 12090

East Asian (EAS) AF: 0.000398 AC: 9 AN: 22592

South Asian (SAS) AF: 0.0000330 AC: 1 AN: 30282

European-Finnish (FIN) AF: 0.000346 AC: 11 AN: 31794

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2596

European-Non Finnish (NFE) AF: 0.0000922 AC: 80 AN: 867370

Other (OTH) AF: 0.000302 AC: 12 AN: 39774

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

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	0.090
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	3.9
DANN	Benign	0.86
DEOGEN2	Benign	0.0071	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.28	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.92
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.067
Sift	Benign	0.073	T
Sift4G	Benign	0.099	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.24		Gain of glycosylation at A52 (P = 0.0139)
MVP		0.33
MPC		0.37
ClinPred		0.057	T
GERP RS		-5.6
PromoterAI		-0.080	Neutral
Varity_R		0.073
gMVP		0.080
Mutation Taster		=96/4	polymorphism

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: rs1644065016; hg19: chr1-46269721;