4-9782291-C-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000798.5(DRD5):​c.262C>T​(p.Leu88Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00727 in 1,614,012 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0050 ( 12 hom., cov: 34)
Exomes 𝑓: 0.0075 ( 55 hom. )

Consequence

DRD5
NM_000798.5 missense

Scores

12
6

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.47

Publications

12 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]
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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.020658612).
BP6
Variant 4-9782291-C-T is Benign according to our data. Variant chr4-9782291-C-T is described in ClinVar as [Benign]. Clinvar id is 592325.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High Homozygotes in GnomAd4 at 12 Unknown gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DRD5NM_000798.5 linkc.262C>T p.Leu88Phe missense_variant Exon 1 of 1 ENST00000304374.4 NP_000789.1 P21918

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DRD5ENST00000304374.4 linkc.262C>T p.Leu88Phe missense_variant Exon 1 of 1 6 NM_000798.5 ENSP00000306129.2 P21918
SLC2A9ENST00000503803.5 linkn.386-2226G>A intron_variant Intron 3 of 3 3
SLC2A9ENST00000508585.5 linkn.182-10922G>A intron_variant Intron 1 of 1 3

Frequencies

GnomAD3 genomes
AF:
0.00503
AC:
766
AN:
152274
Hom.:
12
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00181
Gnomad AMI
AF:
0.0110
Gnomad AMR
AF:
0.00707
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00145
Gnomad FIN
AF:
0.000658
Gnomad MID
AF:
0.0190
Gnomad NFE
AF:
0.00780
Gnomad OTH
AF:
0.0105
GnomAD2 exomes
AF:
0.00466
AC:
1171
AN:
251058
AF XY:
0.00463
show subpopulations
Gnomad AFR exome
AF:
0.00142
Gnomad AMR exome
AF:
0.00734
Gnomad ASJ exome
AF:
0.000397
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000924
Gnomad NFE exome
AF:
0.00714
Gnomad OTH exome
AF:
0.00604
GnomAD4 exome
AF:
0.00750
AC:
10961
AN:
1461620
Hom.:
55
Cov.:
31
AF XY:
0.00727
AC XY:
5287
AN XY:
727120
show subpopulations
African (AFR)
AF:
0.00105
AC:
35
AN:
33470
American (AMR)
AF:
0.00776
AC:
347
AN:
44714
Ashkenazi Jewish (ASJ)
AF:
0.000191
AC:
5
AN:
26132
East Asian (EAS)
AF:
0.000428
AC:
17
AN:
39700
South Asian (SAS)
AF:
0.000986
AC:
85
AN:
86242
European-Finnish (FIN)
AF:
0.000955
AC:
51
AN:
53402
Middle Eastern (MID)
AF:
0.000870
AC:
5
AN:
5744
European-Non Finnish (NFE)
AF:
0.00904
AC:
10052
AN:
1111840
Other (OTH)
AF:
0.00603
AC:
364
AN:
60376
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.483
Heterozygous variant carriers
0
779
1558
2338
3117
3896
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
408
816
1224
1632
2040
<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:
0.00503
AC:
766
AN:
152392
Hom.:
12
Cov.:
34
AF XY:
0.00454
AC XY:
338
AN XY:
74528
show subpopulations
African (AFR)
AF:
0.00180
AC:
75
AN:
41602
American (AMR)
AF:
0.00712
AC:
109
AN:
15306
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5182
South Asian (SAS)
AF:
0.00145
AC:
7
AN:
4834
European-Finnish (FIN)
AF:
0.000658
AC:
7
AN:
10632
Middle Eastern (MID)
AF:
0.0204
AC:
6
AN:
294
European-Non Finnish (NFE)
AF:
0.00779
AC:
530
AN:
68042
Other (OTH)
AF:
0.0104
AC:
22
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.497
Heterozygous variant carriers
0
44
88
131
175
219
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00616
Hom.:
1
Bravo
AF:
0.00536
TwinsUK
AF:
0.0113
AC:
42
ALSPAC
AF:
0.00908
AC:
35
ESP6500AA
AF:
0.00159
AC:
7
ESP6500EA
AF:
0.00767
AC:
66
ExAC
AF:
0.00452
AC:
549
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.00758
EpiControl
AF:
0.00848

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Jul 27, 2017
Eurofins Ntd Llc (ga)
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

DRD5-related disorder Benign:1
Oct 31, 2019
PreventionGenetics, part of Exact Sciences
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

This variant is classified as 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
AlphaMissense
Benign
0.18
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Uncertain
-0.060
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.43
T
Eigen
Uncertain
0.60
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Uncertain
0.97
D
MetaRNN
Benign
0.021
T
MetaSVM
Benign
-0.50
T
MutationAssessor
Benign
1.9
L
PhyloP100
4.5
PrimateAI
Uncertain
0.66
T
PROVEAN
Uncertain
-3.4
D
REVEL
Uncertain
0.52
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.030
D
Polyphen
1.0
D
Vest4
0.89
MVP
0.60
MPC
0.89
ClinPred
0.024
T
GERP RS
4.1
Varity_R
0.86
gMVP
0.73
Mutation Taster
=38/62
disease causing

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

Other links and lift over

dbSNP: rs148402761; hg19: chr4-9783915; COSMIC: COSV58577775; API