13-46837850-A-G

Position:

• chr13-46837850-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000621.5(HTR2A):​c.614-2211T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,198 control chromosomes in the GnomAD database, including 37,960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.69 (37960 hom., cov: 34)
• Consequence: HTR2A NM_000621.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: 1.48

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 13-46837850-A-G is Benign according to our data. Variant chr13-46837850-A-G is described in ClinVar as [Benign]. Clinvar id is 226025.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HTR2A	NM_000621.5	c.614-2211T>C		intron_variant		ENST00000542664.4	NP_000612.1
HTR2A	NM_001378924.1	c.614-2211T>C		intron_variant			NP_001365853.1
HTR2A	NM_001165947.5	c.125-2211T>C		intron_variant			NP_001159419.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR2A	ENST00000542664.4	c.614-2211T>C		intron_variant		1	NM_000621.5	ENSP00000437737.1
HTR2A	ENST00000543956.5	c.125-2211T>C		intron_variant		1		ENSP00000441861.2

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104370 AN: 152080 Hom.: 37922 Cov.: 34

Gnomad AFR AF: 0.927

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.695

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

GnomAD4 genome AF: 0.686 AC: 104464 AN: 152198 Hom.: 37960 Cov.: 34 AF XY: 0.680 AC XY: 50595 AN XY: 74396

Gnomad4 AFR AF: 0.927

Gnomad4 AMR AF: 0.686

Gnomad4 ASJ AF: 0.719

Gnomad4 EAS AF: 0.740

Gnomad4 SAS AF: 0.591

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.578

Gnomad4 OTH AF: 0.692

Alfa AF: 0.604 Hom.: 10270

Bravo AF: 0.719

Asia WGS AF: 0.671 AC: 2336 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 09, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Major depressive disorder, response to citalopram therapy in Other:1

drug response, no assertion criteria provided

literature only

OMIM

May 01, 2006

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	12
DANN	Benign	0.73

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: rs7997012; hg19: chr13-47411985;