GeneBe

rs117836900

Variant names:

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_015057.5(MYCBP2):ā€‹c.13755G>Cā€‹(p.Gln4585His) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000685 in 1,459,154 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

MYCBP2
NM_015057.5 missense, splice_region

Scores

5
7
5
Splicing: ADA: 1.000
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.57
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-AS1 (HGNC:41023): (MYCBP2 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. Scorers claiming Uncertain: max_spliceai. No scorers claiming Benign.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYCBP2NM_015057.5 linkc.13755G>C p.Gln4585His missense_variant, splice_region_variant Exon 81 of 83 ENST00000544440.7 NP_055872.4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYCBP2ENST00000544440.7 linkc.13755G>C p.Gln4585His missense_variant, splice_region_variant Exon 81 of 83 1 NM_015057.5 ENSP00000444596.2 O75592-1
ENSG00000283208ENST00000638147.2 linkc.566-23707C>G intron_variant Intron 3 of 4 5 ENSP00000490953.2 A0A1B0GWJ7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459154
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
726032
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.86
BayesDel_addAF
Uncertain
0.082
D
BayesDel_noAF
Benign
-0.12
CADD
Pathogenic
29
DANN
Uncertain
0.99
Eigen
Pathogenic
0.77
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.93
.;D;D
M_CAP
Benign
0.019
T
MetaRNN
Uncertain
0.45
T;T;T
MetaSVM
Benign
-0.78
T
PrimateAI
Pathogenic
0.88
D
PROVEAN
Uncertain
-3.7
D;D;.
REVEL
Benign
0.22
Sift
Uncertain
0.024
D;D;.
Sift4G
Uncertain
0.0020
D;D;D
Vest4
0.84
MutPred
0.32
Gain of catalytic residue at R4545 (P = 3e-04);Gain of catalytic residue at R4545 (P = 3e-04);.;
MVP
0.56
MPC
1.8
ClinPred
0.99
D
GERP RS
5.7

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.99
SpliceAI score (max)
0.41
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.41
Position offset: 0

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: chr13-77625946; API