4-9782215-C-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_000798.5(DRD5):​c.186C>A​(p.Cys62Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0004 in 1,611,896 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00042 ( 13 hom. )

Consequence

DRD5
NM_000798.5 stop_gained

Scores

2
5

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.838
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6
Variant 4-9782215-C-A is Benign according to our data. Variant chr4-9782215-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3043073.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High AC in GnomAd4 at 32 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DRD5NM_000798.5 linkuse as main transcriptc.186C>A p.Cys62Ter stop_gained 1/1 ENST00000304374.4 NP_000789.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DRD5ENST00000304374.4 linkuse as main transcriptc.186C>A p.Cys62Ter stop_gained 1/1 NM_000798.5 ENSP00000306129 P1
SLC2A9ENST00000503803.5 linkuse as main transcriptn.386-2150G>T intron_variant, non_coding_transcript_variant 3
SLC2A9ENST00000508585.5 linkuse as main transcriptn.182-10846G>T intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.000210
AC:
32
AN:
152260
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000723
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00558
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000884
AC:
220
AN:
248814
Hom.:
4
AF XY:
0.00116
AC XY:
156
AN XY:
134644
show subpopulations
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 SAS exome
AF:
0.00695
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000356
Gnomad OTH exome
AF:
0.000826
GnomAD4 exome
AF:
0.000419
AC:
612
AN:
1459518
Hom.:
13
Cov.:
31
AF XY:
0.000620
AC XY:
450
AN XY:
725934
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000385
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00664
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.000432
GnomAD4 genome
AF:
0.000210
AC:
32
AN:
152378
Hom.:
0
Cov.:
34
AF XY:
0.000322
AC XY:
24
AN XY:
74514
show subpopulations
Gnomad4 AFR
AF:
0.0000721
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00559
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000746
Hom.:
0
Bravo
AF:
0.0000567
ExAC
AF:
0.000939
AC:
114
Asia WGS
AF:
0.00173
AC:
7
AN:
3478
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

DRD5-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesDec 06, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Uncertain
0.020
CADD
Pathogenic
26
DANN
Uncertain
0.98
Eigen
Benign
-0.59
Eigen_PC
Benign
-0.94
FATHMM_MKL
Benign
0.47
N
MutationTaster
Benign
1.0
D
Vest4
0.72
GERP RS
-2.0

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.

Other links and lift over

dbSNP: rs570059380; hg19: chr4-9783839; API