13-46864957-T-C

Position:

• chr13-46864957-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000621.5(HTR2A):​c.613+27433A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 152,082 control chromosomes in the GnomAD database, including 53,710 homozygotes. 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: 𝑓 0.83 (53710 hom., cov: 31)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HTR2A	NM_000621.5	c.613+27433A>G		intron_variant		ENST00000542664.4
HTR2A	NM_001165947.5	c.124+27433A>G		intron_variant
HTR2A	NM_001378924.1	c.613+27433A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HTR2A	ENST00000542664.4	c.613+27433A>G		intron_variant		1	NM_000621.5	P1
HTR2A	ENST00000543956.5	c.124+27433A>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.832 AC: 126373 AN: 151964 Hom.: 53682 Cov.: 31

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.912

Gnomad AMR AF: 0.878

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.966

Gnomad SAS AF: 0.916

Gnomad FIN AF: 0.919

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.910

Gnomad OTH AF: 0.830

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

GnomAD4 genome AF: 0.831 AC: 126456 AN: 152082 Hom.: 53710 Cov.: 31 AF XY: 0.835 AC XY: 62070 AN XY: 74348

Gnomad4 AFR AF: 0.632

Gnomad4 AMR AF: 0.878

Gnomad4 ASJ AF: 0.858

Gnomad4 EAS AF: 0.966

Gnomad4 SAS AF: 0.915

Gnomad4 FIN AF: 0.919

Gnomad4 NFE AF: 0.910

Gnomad4 OTH AF: 0.831

Alfa AF: 0.882 Hom.: 23109

Bravo AF: 0.819

Asia WGS AF: 0.920 AC: 3198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.6
DANN	Benign	0.67

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

Other links and lift over

dbSNP: rs2760347; hg19: chr13-47439092;