1-45824425-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_015112.3(MAST2):​c.178-8C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,582,822 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0066 ( 12 hom., cov: 32)
Exomes 𝑓: 0.00062 ( 15 hom. )

Consequence

MAST2
NM_015112.3 splice_region, splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.001740
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.615
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 1-45824425-C-G is Benign according to our data. Variant chr1-45824425-C-G is described in ClinVar as [Benign]. Clinvar id is 716802.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00662 (1008/152254) while in subpopulation AFR AF= 0.0234 (972/41550). AF 95% confidence interval is 0.0222. There are 12 homozygotes in gnomad4. There are 467 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MAST2NM_015112.3 linkuse as main transcriptc.178-8C>G splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000361297.7 NP_055927.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MAST2ENST00000361297.7 linkuse as main transcriptc.178-8C>G splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_015112.3 ENSP00000354671 Q6P0Q8-1
MAST2ENST00000470809.1 linkuse as main transcriptn.147-8C>G splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00657
AC:
1000
AN:
152136
Hom.:
12
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0233
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00164
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00430
GnomAD3 exomes
AF:
0.00157
AC:
369
AN:
234962
Hom.:
6
AF XY:
0.00123
AC XY:
157
AN XY:
127718
show subpopulations
Gnomad AFR exome
AF:
0.0231
Gnomad AMR exome
AF:
0.000334
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000183
Gnomad OTH exome
AF:
0.00125
GnomAD4 exome
AF:
0.000617
AC:
882
AN:
1430568
Hom.:
15
Cov.:
29
AF XY:
0.000509
AC XY:
361
AN XY:
708802
show subpopulations
Gnomad4 AFR exome
AF:
0.0239
Gnomad4 AMR exome
AF:
0.000419
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000122
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000155
Gnomad4 OTH exome
AF:
0.00124
GnomAD4 genome
AF:
0.00662
AC:
1008
AN:
152254
Hom.:
12
Cov.:
32
AF XY:
0.00627
AC XY:
467
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.0234
Gnomad4 AMR
AF:
0.00163
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00426
Alfa
AF:
0.00208
Hom.:
1
Bravo
AF:
0.00798
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJun 05, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.77
CADD
Benign
3.1
DANN
Benign
0.51

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0017
dbscSNV1_RF
Benign
0.030
SpliceAI score (max)
0.050
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs116664070; hg19: chr1-46290097; API