chr13-46876300-T-A

Variant names:

• chr13-46876300-T-A
• rs2770302
• NM_000621.5:c.613+16090A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000621.5(HTR2A):​c.613+16090A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 151,158 control chromosomes in the GnomAD database, including 48,782 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 0.80 (48782 hom., cov: 28)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR2A	NM_000621.5	c.613+16090A>T		intron_variant	Intron 3 of 3	ENST00000542664.4	NP_000612.1
HTR2A	NM_001378924.1	c.613+16090A>T		intron_variant	Intron 3 of 3		NP_001365853.1
HTR2A	NM_001165947.5	c.124+16090A>T		intron_variant	Intron 2 of 2		NP_001159419.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR2A	ENST00000542664.4	c.613+16090A>T		intron_variant	Intron 3 of 3	1	NM_000621.5	ENSP00000437737.1
HTR2A	ENST00000543956.5	c.124+16090A>T		intron_variant	Intron 2 of 2	1		ENSP00000441861.2

Frequencies

GnomAD3 genomes AF: 0.800 AC: 120838 AN: 151046 Hom.: 48749 Cov.: 28

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.728

Gnomad FIN AF: 0.721

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.800 AC: 120921 AN: 151158 Hom.: 48782 Cov.: 28 AF XY: 0.796 AC XY: 58794 AN XY: 73830

African (AFR) AF: 0.911 AC: 37564 AN: 41246

American (AMR) AF: 0.789 AC: 11994 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 2925 AN: 3468

East Asian (EAS) AF: 0.722 AC: 3711 AN: 5138

South Asian (SAS) AF: 0.728 AC: 3481 AN: 4780

European-Finnish (FIN) AF: 0.721 AC: 7356 AN: 10202

Middle Eastern (MID) AF: 0.808 AC: 236 AN: 292

European-Non Finnish (NFE) AF: 0.756 AC: 51263 AN: 67836

Other (OTH) AF: 0.809 AC: 1694 AN: 2094

Alfa AF: 0.693 Hom.: 1946

Bravo AF: 0.808

Asia WGS AF: 0.730 AC: 2538 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.80
PhyloP100		0.021
Mutation Taster		=100/0	polymorphism (auto)

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: rs2770302; hg19: chr13-47450435;