chr1-46021880-G-A

Variant names:

• chr1-46021880-G-A
• rs2275426
• NM_015112.3:c.1291-70G>A

Variant summary

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

The NM_015112.3(MAST2):​c.1291-70G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 1,536,424 control chromosomes in the GnomAD database, including 153,473 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 (15198 hom., cov: 32)
  • Exomes 𝑓: 0.44 (138275 hom.)
• Consequence: MAST2 NM_015112.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.731
• Publications: 24 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 (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAST2	NM_015112.3	c.1291-70G>A		intron_variant	Intron 11 of 28	ENST00000361297.7	NP_055927.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAST2	ENST00000361297.7	c.1291-70G>A		intron_variant	Intron 11 of 28	1	NM_015112.3	ENSP00000354671.2
MAST2	ENST00000674079.1	c.862-70G>A		intron_variant	Intron 9 of 26			ENSP00000501318.1
MAST2	ENST00000372008.6	c.946-70G>A		intron_variant	Intron 9 of 19	5		ENSP00000361078.2
MAST2	ENST00000467367.5	n.-85G>A		upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67601 AN: 151652 Hom.: 15213 Cov.: 32

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.441

GnomAD4 exome AF: 0.444 AC: 615107 AN: 1384654 Hom.: 138275 AF XY: 0.444 AC XY: 306048 AN XY: 689652

African (AFR) AF: 0.412 AC: 13182 AN: 31978

American (AMR) AF: 0.532 AC: 22811 AN: 42888

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 11135 AN: 24092

East Asian (EAS) AF: 0.642 AC: 25138 AN: 39140

South Asian (SAS) AF: 0.437 AC: 35280 AN: 80794

European-Finnish (FIN) AF: 0.419 AC: 21876 AN: 52272

Middle Eastern (MID) AF: 0.406 AC: 2243 AN: 5518

European-Non Finnish (NFE) AF: 0.436 AC: 457572 AN: 1050398

Other (OTH) AF: 0.449 AC: 25870 AN: 57574

GnomAD4 genome AF: 0.445 AC: 67581 AN: 151770 Hom.: 15198 Cov.: 32 AF XY: 0.446 AC XY: 33070 AN XY: 74166

African (AFR) AF: 0.420 AC: 17388 AN: 41376

American (AMR) AF: 0.488 AC: 7443 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1620 AN: 3468

East Asian (EAS) AF: 0.627 AC: 3209 AN: 5122

South Asian (SAS) AF: 0.446 AC: 2145 AN: 4812

European-Finnish (FIN) AF: 0.411 AC: 4329 AN: 10530

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.442 AC: 29997 AN: 67902

Other (OTH) AF: 0.435 AC: 917 AN: 2110

Alfa AF: 0.443 Hom.: 6739

Bravo AF: 0.451

Asia WGS AF: 0.522 AC: 1813 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0030
DANN	Benign	0.60
PhyloP100		-0.73
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: rs2275426; hg19: chr1-46487552; COSMIC: COSV63616189; COSMIC: COSV63616189;