Variant chr21-36200347-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001320714.2(DOP1B):c.337C>T(p.Leu113Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000562 in 1,602,256 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

DOP1B
NM_001320714.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.58

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]

DOP1B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOP1B	NM_001320714.2 linkuse as main transcript	c.337C>T	p.Leu113Phe	missense_variant	4/37	ENST00000691173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOP1B	ENST00000691173.1 linkuse as main transcript	c.337C>T	p.Leu113Phe	missense_variant	4/37		NM_001320714.2	P1	Q9Y3R5-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000209

AC:

AN:

239612

Hom.:

AF XY:

0.00

AC XY:

AN XY:

130142

show subpopulations

Gnomad AFR exome

AF:

0.0000632

Gnomad AMR exome

AF:

0.000127

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000414

AC:

AN:

1450042

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721250

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000120

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000659

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.00000824

AC:

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 submitter

clinical testing

Ambry Genetics

Aug 16, 2022

The c.337C>T (p.L113F) 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 337, causing the leucine (L) at amino acid position 113 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

Pathogenic

0.92

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

DANN

Uncertain

0.99

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.90

LIST_S2

Pathogenic

0.99

D;T

M_CAP

Benign

0.025

MetaRNN

Uncertain

0.56

D;D

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.9

D;D

REVEL

Uncertain

0.31

Sift

Benign

0.43

T;D

Sift4G

Benign

0.13

T;D

Polyphen

1.0

.;D

Vest4

0.49

MVP

0.47

MPC

0.43

ClinPred

0.85

GERP RS

5.5

Varity_R

0.62

gMVP

0.59

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