13-46834990-AG-GA

Variant names:

• chr13-46834990-AG-GA
• NM_000621.5:c.1262_1263delCTinsTC
• HTR2A p.Ser421Phe

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_000621.5(HTR2A):​c.1262_1263delCTinsTC​(p.Ser421Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, 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)
• Consequence: HTR2A NM_000621.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.51
• Publications: 0 publications found

Genes affected

HTR2A (HGNC:5293): (5-hydroxytryptamine receptor 2A) This gene encodes one of the receptors for serotonin, a neurotransmitter with many roles. Mutations in this gene are associated with susceptibility to schizophrenia and obsessive-compulsive disorder, and are also associated with response to the antidepressant citalopram in patients with major depressive disorder (MDD). MDD patients who also have a mutation in intron 2 of this gene show a significantly reduced response to citalopram as this antidepressant downregulates expression of this gene. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000621.5. 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
	HTR2A	NM_000621.5	MANE Select	c.1262_1263delCTinsTC	p.Ser421Phe	missense	N/A	NP_000612.1	P28223-1
	HTR2A	NM_001378924.1		c.1262_1263delCTinsTC	p.Ser421Phe	missense	N/A	NP_001365853.1	P28223-1
	HTR2A	NM_001165947.5		c.773_774delCTinsTC	p.Ser258Phe	missense	N/A	NP_001159419.2	A0A7P0PKG8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HTR2A	ENST00000542664.4	TSL:1 MANE Select	c.1262_1263delCTinsTC	p.Ser421Phe	missense	N/A	ENSP00000437737.1	P28223-1
	HTR2A	ENST00000543956.5	TSL:1	c.773_774delCTinsTC	p.Ser258Phe	missense	N/A	ENSP00000441861.2	A0A7P0PKG8
	HTR2A	ENST00000941626.1		c.1262_1263delCTinsTC	p.Ser421Phe	missense	N/A	ENSP00000611685.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.5

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr13-47409125;