Variant 21-36212008-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001320714.2(DOP1B):c.815C>A(p.Ser272Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000787 in 1,614,092 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00094 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00077 ( 13 hom. )

Consequence

DOP1B
NM_001320714.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.43

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008208245).

BP6

Variant 21-36212008-C-A is Benign according to our data. Variant chr21-36212008-C-A is described in ClinVar as [Benign]. Clinvar id is 712656.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000939 (143/152274) while in subpopulation EAS AF= 0.0244 (126/5172). AF 95% confidence interval is 0.0209. There are 0 homozygotes in gnomad4. There are 77 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOP1B	NM_001320714.2 linkuse as main transcript	c.815C>A	p.Ser272Tyr	missense_variant	7/37	ENST00000691173.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOP1B	ENST00000691173.1 linkuse as main transcript	c.815C>A	p.Ser272Tyr	missense_variant	7/37		NM_001320714.2	P1	Q9Y3R5-1

Frequencies

GnomAD3 genomes

AF:

0.000940

AC:

143

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0243

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00212

AC:

532

AN:

251194

Hom.:

AF XY:

0.00193

AC XY:

262

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.0280

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000771

AC:

1127

AN:

1461818

Hom.:

Cov.:

AF XY:

0.000730

AC XY:

531

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.0245

Gnomad4 SAS exome

AF:

0.000441

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.00149

GnomAD4 genome

AF:

0.000939

AC:

143

AN:

152274

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0244

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00125

Hom.:

Bravo

AF:

0.00122

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.00195

AC:

237

Asia WGS

AF:

0.00866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.60

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.27

Eigen

Benign

-0.021

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.80

MetaRNN

Benign

0.0082

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.11

Sift

Uncertain

0.024

Sift4G

Benign

0.082

Polyphen

0.93

Vest4

0.25

MVP

0.39

MPC

0.44

ClinPred

0.091

GERP RS

4.3

Varity_R

0.17

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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