dbSNP rs2227849: DRD5:p.Gly110Glu (chr4-9782358-G-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_000798.5(DRD5):c.329G>A(p.Gly110Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 34)

Consequence

DRD5
NM_000798.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.43

Publications

8 publications found

Variant links:

Genes affected

DRD5 (HGNC:3026): (dopamine receptor D5) This gene encodes the D5 subtype of the dopamine receptor. The D5 subtype is a G-protein coupled receptor which stimulates adenylyl cyclase. This receptor is expressed in neurons in the limbic regions of the brain. It has a 10-fold higher affinity for dopamine than the D1 subtype. Pseudogenes related to this gene reside on chromosomes 1 and 2. [provided by RefSeq, Jul 2008]

DRD5 links:

SLC2A9 (HGNC:13446): (solute carrier family 2 member 9) This gene encodes a member of the SLC2A facilitative glucose transporter family. Members of this family play a significant role in maintaining glucose homeostasis. The encoded protein may play a role in the development and survival of chondrocytes in cartilage matrices. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

SLC2A9 Gene-Disease associations (from GenCC):

hypouricemia, renal, 2
Inheritance: AD, AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
hereditary renal hypouricemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SLC2A9 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.898

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000798.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD5	NM_000798.5	MANE Select	c.329G>A	p.Gly110Glu	missense	Exon 1 of 1	NP_000789.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
DRD5	ENST00000304374.4	TSL:6 MANE Select	c.329G>A	p.Gly110Glu	missense	Exon 1 of 1	ENSP00000306129.2
SLC2A9	ENST00000503803.5	TSL:3	n.386-2293C>T		intron	N/A
SLC2A9	ENST00000508585.5	TSL:3	n.182-10989C>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

250862

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000930

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.000123

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.68

M_CAP

Benign

0.031

MetaRNN

Pathogenic

0.90

MetaSVM

Uncertain

-0.20

MutationAssessor

Pathogenic

3.0

PhyloP100

9.4

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-5.4

REVEL

Pathogenic

0.66

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.025

Polyphen

0.82

Vest4

0.95

MVP

0.51

MPC

0.88

ClinPred

1.0

GERP RS

4.1

Varity_R

0.91

gMVP

0.95

Mutation Taster

=13/87

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over