4-9781804-G-T

Variant names:

• chr4-9781804-G-T
• rs2076907
• NM_000798.5:c.-226G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000798.5(DRD5):​c.-226G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DRD5 NM_000798.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.97
• Publications: 11 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: AR, AD, SD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• hereditary renal hypouricemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD5	NM_000798.5	MANE Select	c.-226G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 1	NP_000789.1	P21918
	DRD5	NM_000798.5	MANE Select	c.-226G>T		5_prime_UTR	Exon 1 of 1	NP_000789.1	P21918

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD5	ENST00000304374.4	TSL:6 MANE Select	c.-226G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 1	ENSP00000306129.2	P21918
	DRD5	ENST00000304374.4	TSL:6 MANE Select	c.-226G>T		5_prime_UTR	Exon 1 of 1	ENSP00000306129.2	P21918
	DRD5	ENST00000888644.1		c.-226G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 2	ENSP00000558703.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 270152 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 136924

African (AFR) AF: 0.00 AC: 0 AN: 7230

American (AMR) AF: 0.00 AC: 0 AN: 9010

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9674

East Asian (EAS) AF: 0.00 AC: 0 AN: 23112

South Asian (SAS) AF: 0.00 AC: 0 AN: 5158

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21978

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1368

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 174940

Other (OTH) AF: 0.00 AC: 0 AN: 17682

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 3088

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.56
PhyloP100		-3.0
PromoterAI		-0.019	Neutral

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: rs2076907; hg19: chr4-9783428;