Variant chr13-77055554-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_015057.5(MYCBP2):c.13647+4T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00262 in 1,612,264 control chromosomes in the GnomAD database, including 6 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 6 hom. )

Consequence

MYCBP2
NM_015057.5 splice_region, intron

Scores

Splicing: ADA: 0.0001324

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.22

Variant links:

Genes affected

MYCBP2 (HGNC:23386): (MYC binding protein 2) This gene encodes an E3 ubiquitin-protein ligase and member of the PHR (Phr1/MYCBP2, highwire and RPM-1) family of proteins. The encoded protein plays a role in axon guidance and synapse formation in the developing nervous system. In mammalian cells, this protein regulates the cAMP and mTOR signaling pathways, and may additionally regulate autophagy. Reduced expression of this gene has been observed in acute lymphoblastic leukemia patients and a mutation in this gene has been identified in patients with a rare inherited vision defect. [provided by RefSeq, Mar 2017]

MYCBP2 links:

ENSG00000283208 (HGNC:):

ENSG00000283208 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 13-77055554-A-T is Benign according to our data. Variant chr13-77055554-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 718182.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 364 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYCBP2	NM_015057.5 linkuse as main transcript	c.13647+4T>A		splice_region_variant, intron_variant		ENST00000544440.7	NP_055872.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYCBP2	ENST00000544440.7 linkuse as main transcript	c.13647+4T>A		splice_region_variant, intron_variant		1	NM_015057.5	ENSP00000444596.2		O75592-1
ENSG00000283208	ENST00000638147.2 linkuse as main transcript	c.566-19964A>T		intron_variant		5		ENSP00000490953.2		A0A1B0GWJ7

Frequencies

GnomAD3 genomes

AF:

0.00239

AC:

364

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00419

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00220

AC:

546

AN:

248350

Hom.:

AF XY:

0.00222

AC XY:

299

AN XY:

134480

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00428

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000230

Gnomad FIN exome

AF:

0.00178

Gnomad NFE exome

AF:

0.00360

Gnomad OTH exome

AF:

0.00198

GnomAD4 exome

AF:

0.00264

AC:

3858

AN:

1459958

Hom.:

Cov.:

AF XY:

0.00262

AC XY:

1901

AN XY:

726344

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.00107

Gnomad4 ASJ exome

AF:

0.00387

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000569

Gnomad4 FIN exome

AF:

0.00187

Gnomad4 NFE exome

AF:

0.00305

Gnomad4 OTH exome

AF:

0.00254

GnomAD4 genome

AF:

0.00239

AC:

364

AN:

152306

Hom.:

Cov.:

AF XY:

0.00213

AC XY:

159

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000481

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.00433

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00419

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00319

Hom.:

Bravo

AF:

0.00234

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00289

EpiControl

AF:

0.00350

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 16, 2018

- -

MYCBP2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 26, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00013

dbscSNV1_RF

Benign

0.048

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