11-637349-GCGCGGGCCGGC-GCGCGGGCCGGCCGCGGGCCGGC

Variant names:

• chr11-637349-G-GCGCGGGCCGGC
• rs1279080134
• NM_000797.4:c.52_62dupCCGGCCGCGGG

Variant summary

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

The NM_000797.4(DRD4):​c.52_62dupCCGGCCGCGGG​(p.Ala22ArgfsTer40) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000175 in 1,140,180 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: DRD4 NM_000797.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0590
• Publications: 0 publications found

Genes affected

DRD4 (HGNC:3025): (dopamine receptor D4) This gene encodes the D4 subtype of the dopamine receptor. The D4 subtype is a G-protein coupled receptor which inhibits adenylyl cyclase. It is a target for drugs which treat schizophrenia and Parkinson disease. Mutations in this gene have been associated with various behavioral phenotypes, including autonomic nervous system dysfunction, attention deficit/hyperactivity disorder, and the personality trait of novelty seeking. This gene contains a polymorphic number (2-10 copies) of tandem 48 nt repeats; the sequence shown contains four repeats. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000797.4. 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
	DRD4	NM_000797.4	MANE Select	c.52_62dupCCGGCCGCGGG	p.Ala22ArgfsTer40	frameshift	Exon 1 of 4	NP_000788.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DRD4	ENST00000176183.6	TSL:1 MANE Select	c.52_62dupCCGGCCGCGGG	p.Ala22ArgfsTer40	frameshift	Exon 1 of 4	ENSP00000176183.5	P21917

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000175 AC: 2 AN: 1140180 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 548226

African (AFR) AF: 0.00 AC: 0 AN: 22650

American (AMR) AF: 0.00 AC: 0 AN: 8178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14678

East Asian (EAS) AF: 0.00 AC: 0 AN: 25528

South Asian (SAS) AF: 0.00 AC: 0 AN: 35612

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3130

European-Non Finnish (NFE) AF: 0.00000209 AC: 2 AN: 959068

Other (OTH) AF: 0.00 AC: 0 AN: 46206

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.059

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1279080134; hg19: chr11-637349;