chr13-46842251-C-T

Variant names:

• chr13-46842251-C-T
• rs17068986
• NM_000621.5:c.614-6612G>A

Variant summary

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

The NM_000621.5(HTR2A):​c.614-6612G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,076 control chromosomes in the GnomAD database, including 1,932 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 0.13 (1932 hom., cov: 32)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 7 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 (EAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR2A	NM_000621.5	c.614-6612G>A		intron_variant	Intron 3 of 3	ENST00000542664.4	NP_000612.1
HTR2A	NM_001378924.1	c.614-6612G>A		intron_variant	Intron 3 of 3		NP_001365853.1
HTR2A	NM_001165947.5	c.125-6612G>A		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.614-6612G>A		intron_variant	Intron 3 of 3	1	NM_000621.5	ENSP00000437737.1
HTR2A	ENST00000543956.5	c.125-6612G>A		intron_variant	Intron 2 of 2	1		ENSP00000441861.2

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19613 AN: 151958 Hom.: 1939 Cov.: 32

Gnomad AFR AF: 0.0432

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.129 AC: 19601 AN: 152076 Hom.: 1932 Cov.: 32 AF XY: 0.133 AC XY: 9894 AN XY: 74302

African (AFR) AF: 0.0432 AC: 1791 AN: 41498

American (AMR) AF: 0.170 AC: 2603 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 480 AN: 3466

East Asian (EAS) AF: 0.512 AC: 2645 AN: 5168

South Asian (SAS) AF: 0.200 AC: 964 AN: 4820

European-Finnish (FIN) AF: 0.147 AC: 1554 AN: 10550

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9091 AN: 67988

Other (OTH) AF: 0.140 AC: 295 AN: 2106

Alfa AF: 0.130 Hom.: 2142

Bravo AF: 0.129

Asia WGS AF: 0.332 AC: 1152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.96
DANN	Benign	0.73
PhyloP100		-1.1
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: rs17068986; hg19: chr13-47416386;