1-45804049-G-C

Position:

• chr1-45804049-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. 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. 14/21 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

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.046587616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAST2	NM_015112.3	c.154G>C	p.Ala52Pro	missense_variant	1/29	ENST00000361297.7	NP_055927.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAST2	ENST00000361297.7	c.154G>C	p.Ala52Pro	missense_variant	1/29	1	NM_015112.3	ENSP00000354671
MAST2	ENST00000470809.1	n.146+16917G>C		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR exome AF: 0.000495

Gnomad4 AMR exome AF: 0.000736

Gnomad4 ASJ exome AF: 0.000662

Gnomad4 EAS exome AF: 0.000398

Gnomad4 SAS exome AF: 0.0000330

Gnomad4 FIN exome AF: 0.000346

Gnomad4 NFE exome AF: 0.0000922

Gnomad4 OTH exome AF: 0.000302

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

The c.154G>C (p.A52P) alteration is located in exon 1 (coding exon 1) of the MAST2 gene. This alteration results from a G to C substitution at nucleotide position 154, causing the alanine (A) at amino acid position 52 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	1.0	N;N
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
Varity_R		0.073
gMVP		0.080

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-46269721;