1-46027788-T-G

Variant names:

• chr1-46027788-T-G
• rs1707336
• NM_015112.3:c.1977T>G

Variant summary

Our verdict is Benign. Variant got -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. 13/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAST2	NM_015112.3	c.1977T>G	p.Ile659Met	missense_variant	Exon 17 of 29	ENST00000361297.7	NP_055927.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAST2	ENST00000361297.7	c.1977T>G	p.Ile659Met	missense_variant	Exon 17 of 29	1	NM_015112.3	ENSP00000354671.2
MAST2	ENST00000674079.1	c.1548T>G	p.Ile516Met	missense_variant	Exon 15 of 27			ENSP00000501318.1
MAST2	ENST00000372008.6	c.1632T>G	p.Ile544Met	missense_variant	Exon 15 of 20	5		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

GnomAD3 exomes AF: 0.466 AC: 116211 AN: 249302 Hom.: 27651 AF XY: 0.461 AC XY: 62400 AN XY: 135254

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 SAS exome AF: 0.437

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

Gnomad4 AFR exome AF: 0.414

Gnomad4 AMR exome AF: 0.534

Gnomad4 ASJ exome AF: 0.463

Gnomad4 EAS exome AF: 0.643

Gnomad4 SAS exome AF: 0.438

Gnomad4 FIN exome AF: 0.419

Gnomad4 NFE exome AF: 0.436

Gnomad4 OTH exome AF: 0.450

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

Gnomad4 AFR AF: 0.421

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.435

Alfa AF: 0.449 Hom.: 38347

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 v4.3

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;T;T
MetaRNN	Benign	0.000052	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L;.;.
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.21	N;N;.
REVEL	Benign	0.29
Sift	Benign	0.46	T;T;.
Sift4G	Benign	0.91	T;T;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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1707336; hg19: chr1-46493460; COSMIC: COSV63616192; COSMIC: COSV63616192;