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GeneBe

21-36200360-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001320714.2(DOP1B):c.350C>T(p.Ala117Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,454,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DOP1B
NM_001320714.2 missense

Scores

4
10
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.69
Variant links:
Genes affected
DOP1B (HGNC:1291): (DOP1 leucine zipper like protein B) Involved in cognition. Located in early endosome membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.881

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DOP1BNM_001320714.2 linkuse as main transcriptc.350C>T p.Ala117Val missense_variant 4/37 ENST00000691173.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DOP1BENST00000691173.1 linkuse as main transcriptc.350C>T p.Ala117Val missense_variant 4/37 NM_001320714.2 P1Q9Y3R5-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000410
AC:
1
AN:
243950
Hom.:
0
AF XY:
0.00000756
AC XY:
1
AN XY:
132332
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000337
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000206
AC:
3
AN:
1454752
Hom.:
0
Cov.:
30
AF XY:
0.00000276
AC XY:
2
AN XY:
723770
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000254
Gnomad4 SAS exome
AF:
0.0000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.01e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

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 GeneticsSep 16, 2021The c.350C>T (p.A117V) alteration is located in exon 4 (coding exon 3) of the DOPEY2 gene. This alteration results from a C to T substitution at nucleotide position 350, causing the alanine (A) at amino acid position 117 to be replaced by a valine (V). 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
Pathogenic
0.81
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
0.080
Cadd
Uncertain
24
Dann
Pathogenic
1.0
Eigen
Uncertain
0.63
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Pathogenic
0.99
D;D
M_CAP
Benign
0.029
D
MetaRNN
Pathogenic
0.88
D;D
MetaSVM
Benign
-0.49
T
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.60
T
PROVEAN
Uncertain
-3.9
D;D
REVEL
Uncertain
0.36
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.013
D;D
Polyphen
1.0
.;D
Vest4
0.91
MutPred
0.70
Loss of methylation at R122 (P = 0.2566);Loss of methylation at R122 (P = 0.2566);
MVP
0.54
MPC
0.71
ClinPred
0.98
D
GERP RS
4.6
Varity_R
0.52
gMVP
0.71

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.

Other links and lift over

dbSNP: rs1424910802; hg19: chr21-37572658; COSMIC: COSV99535999; API