1-46027788-T-G

Variant names:

• chr1-46027788-T-G
• rs1707336
• NM_015112.3:c.1977T>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.1977T>G​(p.Ile659Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,612,994 control chromosomes in the GnomAD database, including 161,246 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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 (15343 hom., cov: 32)
  • Exomes 𝑓: 0.44 (145903 hom.)
• Consequence: MAST2 NM_015112.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391
• Publications: 51 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.243436E-5).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAST2	NM_015112.3	MANE Select	c.1977T>G	p.Ile659Met	missense	Exon 17 of 29	NP_055927.2
	MAST2	NM_001324320.2		c.1998T>G	p.Ile666Met	missense	Exon 18 of 30	NP_001311249.1
	MAST2	NM_001319245.2		c.1977T>G	p.Ile659Met	missense	Exon 17 of 29	NP_001306174.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAST2	ENST00000361297.7	TSL:1 MANE Select	c.1977T>G	p.Ile659Met	missense	Exon 17 of 29	ENSP00000354671.2
	MAST2	ENST00000674079.1		c.1548T>G	p.Ile516Met	missense	Exon 15 of 27	ENSP00000501318.1
	MAST2	ENST00000372008.6	TSL:5	c.1632T>G	p.Ile544Met	missense	Exon 15 of 20	ENSP00000361078.2

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67899 AN: 151920 Hom.: 15358 Cov.: 32

Gnomad AFR AF: 0.422

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.441

GnomAD2 exomes AF: 0.466 AC: 116211 AN: 249302 AF XY: 0.461

Gnomad AFR exome AF: 0.419

Gnomad AMR exome AF: 0.543

Gnomad ASJ exome AF: 0.464

Gnomad EAS exome AF: 0.645

Gnomad FIN exome AF: 0.417

Gnomad NFE exome AF: 0.439

Gnomad OTH exome AF: 0.455

GnomAD4 exome AF: 0.445 AC: 649656 AN: 1460956 Hom.: 145903 Cov.: 37 AF XY: 0.444 AC XY: 322889 AN XY: 726816

African (AFR) AF: 0.414 AC: 13848 AN: 33454

American (AMR) AF: 0.534 AC: 23860 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 12094 AN: 26118

East Asian (EAS) AF: 0.643 AC: 25510 AN: 39682

South Asian (SAS) AF: 0.438 AC: 37719 AN: 86186

European-Finnish (FIN) AF: 0.419 AC: 22389 AN: 53402

Middle Eastern (MID) AF: 0.409 AC: 2359 AN: 5764

European-Non Finnish (NFE) AF: 0.436 AC: 484705 AN: 1111318

Other (OTH) AF: 0.450 AC: 27172 AN: 60352

GnomAD4 genome AF: 0.446 AC: 67879 AN: 152038 Hom.: 15343 Cov.: 32 AF XY: 0.447 AC XY: 33243 AN XY: 74316

African (AFR) AF: 0.421 AC: 17468 AN: 41458

American (AMR) AF: 0.489 AC: 7471 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1623 AN: 3470

East Asian (EAS) AF: 0.629 AC: 3260 AN: 5180

South Asian (SAS) AF: 0.447 AC: 2156 AN: 4818

European-Finnish (FIN) AF: 0.413 AC: 4360 AN: 10560

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.443 AC: 30084 AN: 67962

Other (OTH) AF: 0.435 AC: 920 AN: 2116

Alfa AF: 0.448 Hom.: 51878

Bravo AF: 0.451

TwinsUK AF: 0.426 AC: 1579

ALSPAC AF: 0.441 AC: 1701

ESP6500AA AF: 0.416 AC: 1588

ESP6500EA AF: 0.436 AC: 3613

ExAC AF: 0.461 AC: 55696

Asia WGS AF: 0.523 AC: 1816 AN: 3478

EpiCase AF: 0.448

EpiControl AF: 0.446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.45	T
MetaRNN	Benign	0.000052	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.39
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.29
Sift	Benign	0.46	T
Sift4G	Benign	0.91	T
Polyphen		0.38	B
Vest4		0.25
MPC		1.6
ClinPred		0.041	T
GERP RS		-0.62
Varity_R		0.10
gMVP		0.69
Mutation Taster		=89/11	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: rs1707336; hg19: chr1-46493460; COSMIC: COSV63616192; COSMIC: COSV63616192;