rs1800762

Variant names:

• chr4-9783018-C-A
• rs1800762
• NM_000798.5:c.989C>A

Your query was ambiguous. Multiple possible variants found:

• chr4-9783018-C-A
• chr4-9783018-C-G
• chr4-9783018-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000798.5(DRD5):​c.989C>A​(p.Pro330Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00495 in 1,614,212 control chromosomes in the GnomAD database, including 187 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.011 (38 hom., cov: 33)
  • Exomes 𝑓: 0.0043 (149 hom.)
• Consequence: DRD5 NM_000798.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183
• Publications: 12 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019726157).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0735 is higher than 0.05.

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.989C>A	p.Pro330Gln	missense	Exon 1 of 1	NP_000789.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD5	ENST00000304374.4	TSL:6 MANE Select	c.989C>A	p.Pro330Gln	missense	Exon 1 of 1	ENSP00000306129.2
	SLC2A9	ENST00000503803.5	TSL:3	n.386-2953G>T		intron	N/A
	SLC2A9	ENST00000508585.5	TSL:3	n.182-11649G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1650 AN: 152200 Hom.: 38 Cov.: 33

Gnomad AFR AF: 0.0238

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00438

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0799

Gnomad SAS AF: 0.0306

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.0115 AC: 2886 AN: 251414 AF XY: 0.0115

Gnomad AFR exome AF: 0.0238

Gnomad AMR exome AF: 0.00150

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0851

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000237

Gnomad OTH exome AF: 0.00782

GnomAD4 exome AF: 0.00433 AC: 6329 AN: 1461894 Hom.: 149 Cov.: 36 AF XY: 0.00478 AC XY: 3479 AN XY: 727248

African (AFR) AF: 0.0258 AC: 864 AN: 33480

American (AMR) AF: 0.00152 AC: 68 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0627 AC: 2490 AN: 39700

South Asian (SAS) AF: 0.0252 AC: 2172 AN: 86258

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53420

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5768

European-Non Finnish (NFE) AF: 0.000165 AC: 184 AN: 1112012

Other (OTH) AF: 0.00892 AC: 539 AN: 60396

GnomAD4 genome AF: 0.0109 AC: 1659 AN: 152318 Hom.: 38 Cov.: 33 AF XY: 0.0112 AC XY: 833 AN XY: 74470

African (AFR) AF: 0.0238 AC: 992 AN: 41594

American (AMR) AF: 0.00438 AC: 67 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.0799 AC: 412 AN: 5156

South Asian (SAS) AF: 0.0307 AC: 148 AN: 4828

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68026

Other (OTH) AF: 0.0104 AC: 22 AN: 2114

Alfa AF: 0.00160 Hom.: 1

Bravo AF: 0.0115

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0259 AC: 114

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.0121 AC: 1471

Asia WGS AF: 0.0590 AC: 205 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.024
DANN	Benign	0.83
DEOGEN2	Benign	0.038	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0046	N
LIST_S2	Benign	0.17	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.29	N
PhyloP100		-0.18
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.013
Sift	Benign	0.35	T
Sift4G	Benign	0.64	T
Polyphen		0.0010	B
Vest4		0.029
MPC		0.22
ClinPred		0.0030	T
GERP RS		-2.2
Varity_R		0.023
gMVP		0.42
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1800762; hg19: chr4-9784642; COSMIC: COSV58577303;