Variant rs6314 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000542664.4(HTR2A):c.1354C>T(p.His452Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0872 in 1,613,530 control chromosomes in the GnomAD database, including 6,772 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H452P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.093 ( 721 hom., cov: 32)

Exomes 𝑓: 0.087 ( 6051 hom. )

Consequence

HTR2A
ENST00000542664.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.891

Variant links:

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]

HTR2A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016472638).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
HTR2A	NM_000621.5 linkuse as main transcript	c.1354C>T	p.His452Tyr	missense_variant	4/4	ENST00000542664.4	NP_000612.1
HTR2A	NM_001378924.1 linkuse as main transcript	c.1354C>T	p.His452Tyr	missense_variant	4/4		NP_001365853.1
HTR2A	NM_001165947.5 linkuse as main transcript	c.865C>T	p.His289Tyr	missense_variant	3/3		NP_001159419.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR2A	ENST00000542664.4 linkuse as main transcript	c.1354C>T	p.His452Tyr	missense_variant	4/4	1	NM_000621.5	ENSP00000437737	P1	P28223-1
HTR2A	ENST00000543956.5 linkuse as main transcript	c.865C>T	p.His289Tyr	missense_variant	3/3	1		ENSP00000441861

Frequencies

GnomAD3 genomes

AF:

0.0931

AC:

14163

AN:

152046

Hom.:

717

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.0756

Gnomad ASJ

AF:

0.133

Gnomad EAS

AF:

0.00270

Gnomad SAS

AF:

0.0912

Gnomad FIN

AF:

0.0527

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0898

Gnomad OTH

AF:

0.0954

GnomAD3 exomes

AF:

0.0786

AC:

19741

AN:

251056

Hom.:

911

AF XY:

0.0804

AC XY:

10909

AN XY:

135674

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.0537

Gnomad ASJ exome

AF:

0.130

Gnomad EAS exome

AF:

0.000979

Gnomad SAS exome

AF:

0.0939

Gnomad FIN exome

AF:

0.0473

Gnomad NFE exome

AF:

0.0887

Gnomad OTH exome

AF:

0.0780

GnomAD4 exome

AF:

0.0866

AC:

126548

AN:

1461366

Hom.:

6051

Cov.:

AF XY:

0.0874

AC XY:

63528

AN XY:

727010

show subpopulations

Gnomad4 AFR exome

AF:

0.131

Gnomad4 AMR exome

AF:

0.0549

Gnomad4 ASJ exome

AF:

0.128

Gnomad4 EAS exome

AF:

0.000579

Gnomad4 SAS exome

AF:

0.0957

Gnomad4 FIN exome

AF:

0.0454

Gnomad4 NFE exome

AF:

0.0896

Gnomad4 OTH exome

AF:

0.0908

GnomAD4 genome

AF:

0.0932

AC:

14182

AN:

152164

Hom.:

721

Cov.:

AF XY:

0.0913

AC XY:

6788

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.125

Gnomad4 AMR

AF:

0.0755

Gnomad4 ASJ

AF:

0.133

Gnomad4 EAS

AF:

0.00251

Gnomad4 SAS

AF:

0.0919

Gnomad4 FIN

AF:

0.0527

Gnomad4 NFE

AF:

0.0898

Gnomad4 OTH

AF:

0.0949

Alfa

AF:

0.0920

Hom.:

1185

Bravo

AF:

0.0951

TwinsUK

AF:

0.0885

AC:

328

ALSPAC

AF:

0.0929

AC:

358

ESP6500AA

AF:

0.133

AC:

588

ESP6500EA

AF:

0.0926

AC:

796

ExAC

AF:

0.0789

AC:

9578

Asia WGS

AF:

0.0480

AC:

170

AN:

3478

EpiCase

AF:

0.0980

EpiControl

AF:

0.100

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.59

CADD

Benign

5.4

DANN

Benign

0.89

DEOGEN2

Benign

0.19

T;T;.

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.68

.;T;T

MetaRNN

Benign

0.0016

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

N;N;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.074

Sift

Benign

0.068

T;T;D

Sift4G

Benign

0.11

T;T;D

Polyphen

0.010

B;B;.

Vest4

0.057

MPC

0.33

ClinPred

0.0098

GERP RS

1.7

Varity_R

0.064

gMVP

0.23

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over