dbSNP rs6304: HTR2A:p.Ile197Val (chr13-46892414-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000621.5(HTR2A):c.589A>G(p.Ile197Val) variant causes a missense change. The variant allele was found at a frequency of 0.00386 in 1,614,186 control chromosomes in the GnomAD database, including 203 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.021 ( 105 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 98 hom. )

Consequence

HTR2A
NM_000621.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.02

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031748116).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR2A	NM_000621.5 link	c.589A>G	p.Ile197Val	missense_variant	Exon 3 of 4	ENST00000542664.4	NP_000612.1	P28223-1
HTR2A	NM_001378924.1 link	c.589A>G	p.Ile197Val	missense_variant	Exon 3 of 4		NP_001365853.1
HTR2A	NM_001165947.5 link	c.100A>G	p.Ile34Val	missense_variant	Exon 2 of 3		NP_001159419.2	P28223

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR2A	ENST00000542664.4 link	c.589A>G	p.Ile197Val	missense_variant	Exon 3 of 4	1	NM_000621.5	ENSP00000437737.1		P28223-1
HTR2A	ENST00000543956.5 link	c.100A>G	p.Ile34Val	missense_variant	Exon 2 of 3	1		ENSP00000441861.2		A0A7P0PKG8

Frequencies

GnomAD3 genomes

AF:

0.0208

AC:

3167

AN:

152190

Hom.:

105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00752

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00532

AC:

1338

AN:

251496

Hom.:

AF XY:

0.00377

AC XY:

513

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0730

Gnomad AMR exome

AF:

0.00353

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00209

AC:

3051

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00174

AC XY:

1266

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.0746

Gnomad4 AMR exome

AF:

0.00326

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000737

Gnomad4 OTH exome

AF:

0.00460

GnomAD4 genome

AF:

0.0208

AC:

3174

AN:

152308

Hom.:

105

Cov.:

AF XY:

0.0203

AC XY:

1512

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0724

Gnomad4 AMR

AF:

0.00745

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00919

Hom.:

Bravo

AF:

0.0238

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0624

AC:

275

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00650

AC:

789

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.076

T;T;.

Eigen

Benign

0.041

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.86

.;D;T

MetaRNN

Benign

0.0032

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

0.25

N;N;N

REVEL

Benign

0.11

Sift

Benign

0.74

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.63

P;P;.

Vest4

0.31

MVP

0.43

MPC

1.9

ClinPred

0.030

GERP RS

6.2

Varity_R

0.32

gMVP

0.47

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