20-45406560-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018478.3(DBNDD2):​c.109C>T​(p.Leu37Phe) 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. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

DBNDD2
NM_018478.3 missense

Scores

1
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.172
Variant links:
Genes affected
DBNDD2 (HGNC:15881): (dysbindin domain containing 2) Involved in negative regulation of protein kinase activity. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]
SYS1-DBNDD2 (HGNC:33535): (SYS1-DBNDD2 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription from the neighboring SYS1 Golgi-localized integral membrane protein homolog and dysbindin domain containing 2 (DBNDD2) genes. The read-through transcript includes the majority of exons from each individual gene, but it would be subject to nonsense-mediated mRNA decay (NMD) and is therefore predicted to be non-coding. [provided by RefSeq, Oct 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09416267).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DBNDD2NM_018478.3 linkuse as main transcriptc.109C>T p.Leu37Phe missense_variant 1/4 NP_060948.3 Q9BQY9-1
DBNDD2NM_001048221.3 linkuse as main transcriptc.-9+350C>T intron_variant NP_001041686.1 Q9BQY9-2
DBNDD2NM_001197139.2 linkuse as main transcriptc.-9+539C>T intron_variant NP_001184068.1 Q9BQY9-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SYS1-DBNDD2ENST00000458187.5 linkuse as main transcriptn.293-1900C>T intron_variant 5 ENSP00000457768.1 H3BUS1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 20, 2024The c.109C>T (p.L37F) alteration is located in exon 1 (coding exon 1) of the DBNDD2 gene. This alteration results from a C to T substitution at nucleotide position 109, causing the leucine (L) at amino acid position 37 to be replaced by a phenylalanine (F). 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
0.16
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
17
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0088
T
Eigen
Benign
-0.15
Eigen_PC
Benign
-0.099
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.44
T
M_CAP
Uncertain
0.10
D
MetaRNN
Benign
0.094
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
PROVEAN
Benign
-0.18
N
REVEL
Benign
0.040
Sift
Pathogenic
0.0
D
Sift4G
Benign
0.25
T
Vest4
0.095
MutPred
0.12
Loss of glycosylation at P38 (P = 0.0963);
MVP
0.52
ClinPred
0.36
T
GERP RS
2.0
Varity_R
0.18

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: chr20-44035200; API