Variant 15-94298405-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001385001.1(MCTP2):c.140G>A(p.Arg47His) variant causes a missense change. The variant allele was found at a frequency of 0.000483 in 1,614,164 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R47C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00047 ( 1 hom. )

Consequence

MCTP2
NM_001385001.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.82

Variant links:

Genes affected

MCTP2 (HGNC:25636): (multiple C2 and transmembrane domain containing 2) Enables calcium ion binding activity. Predicted to be involved in regulation of neurotransmitter secretion. Located in cytosol and nucleoplasm. Is integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MCTP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.012650251).

BP6

Variant 15-94298405-G-A is Benign according to our data. Variant chr15-94298405-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 737223.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCTP2	NM_001385001.1 linkuse as main transcript	c.140G>A	p.Arg47His	missense_variant	2/23	ENST00000357742.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCTP2	ENST00000357742.10 linkuse as main transcript	c.140G>A	p.Arg47His	missense_variant	2/23	1	NM_001385001.1	P1	Q6DN12-1

Frequencies

GnomAD3 genomes

AF:

0.000565

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00462

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000474

AC:

119

AN:

251224

Hom.:

AF XY:

0.000390

AC XY:

AN XY:

135764

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00356

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000475

AC:

694

AN:

1461870

Hom.:

Cov.:

AF XY:

0.000462

AC XY:

336

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00363

Gnomad4 NFE exome

AF:

0.000408

Gnomad4 OTH exome

AF:

0.000397

GnomAD4 genome

AF:

0.000565

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.000698

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00462

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000321

Hom.:

Bravo

AF:

0.000189

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000453

AC:

EpiCase

AF:

0.000327

EpiControl

AF:

0.000296

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

-0.080

Cadd

Uncertain

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.018

T;.;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.85

D;D;D

M_CAP

Benign

0.069

MetaRNN

Benign

0.013

T;T;T

MetaSVM

Uncertain

-0.26

MutationTaster

Benign

0.91

D;D;D;D

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.0

N;N;N

REVEL

Benign

0.27

Sift

Uncertain

0.0020

D;D;T

Sift4G

Benign

0.11

T;T;T

Polyphen

0.99

D;D;D

Vest4

0.26

MVP

0.55

MPC

0.12

ClinPred

0.047

GERP RS

5.2

Varity_R

0.12

gMVP

0.41

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over