6-83158615-A-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015018.4(DOP1A):c.6790A>G(p.Ile2264Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 1,603,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

DOP1A
NM_015018.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.73

Publications

0 publications found

Variant links:

Genes affected

DOP1A (HGNC:21194): (DOP1 leucine zipper like protein A) Predicted to be involved in Golgi to endosome transport and endoplasmic reticulum organization. Predicted to be located in Golgi membrane. Predicted to be active in endosome and trans-Golgi network. [provided by Alliance of Genome Resources, Apr 2022]

DOP1A links:

PGM3 (HGNC:8907): (phosphoglucomutase 3) This gene encodes a member of the phosphohexose mutase family. The encoded protein mediates both glycogen formation and utilization by catalyzing the interconversion of glucose-1-phosphate and glucose-6-phosphate. A non-synonymous single nucleotide polymorphism in this gene may play a role in resistance to diabetic nephropathy and neuropathy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2010]

PGM3 Gene-Disease associations (from GenCC):

immunodeficiency 23
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P

PGM3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14596769).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOP1A	NM_015018.4 link	c.6790A>G	p.Ile2264Val	missense_variant	Exon 36 of 39	ENST00000349129.7	NP_055833.2	Q5JWR5B2RWN9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOP1A	ENST00000349129.7 link	c.6790A>G	p.Ile2264Val	missense_variant	Exon 36 of 39	1	NM_015018.4	ENSP00000195654.3		Q5JWR5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000214

AC:

AN:

1451154

Hom.:

Cov.:

AF XY:

0.0000222

AC XY:

AN XY:

721996

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33230

American (AMR)

AF:

0.00

AC:

AN:

44100

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25992

East Asian (EAS)

AF:

0.00

AC:

AN:

39502

South Asian (SAS)

AF:

0.00

AC:

AN:

84522

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53332

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.0000263

AC:

AN:

1104714

Other (OTH)

AF:

0.0000333

AC:

AN:

60042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.436

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 03, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.6763A>G (p.I2255V) alteration is located in exon 36 (coding exon 34) of the DOPEY1 gene. This alteration results from a A to G substitution at nucleotide position 6763, causing the isoleucine (I) at amino acid position 2255 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

Benign

0.10

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.011

.;T;.

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

D;D;.

M_CAP

Benign

0.011

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.34

.;N;.

PhyloP100

8.7

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

0.33

.;N;.

REVEL

Benign

0.13

Sift

Benign

1.0

.;T;.

Sift4G

Benign

1.0

T;T;T

Polyphen

0.080

.;B;.

Vest4

0.39

MutPred

0.21

.;Gain of disorder (P = 0.128);.;

MVP

0.12

MPC

0.26

ClinPred

0.86

GERP RS

5.9

Varity_R

0.055

gMVP

0.13

Mutation Taster

=68/32

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over