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GeneBe

rs6314

Variant summary

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

The NM_000621.5(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. 14/19 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.

Frequency

Genomes: 𝑓 0.093 ( 721 hom., cov: 32)
Exomes 𝑓: 0.087 ( 6051 hom. )

Consequence

HTR2A
NM_000621.5 missense

Scores

17

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]

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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=0.0016472638).
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 UniProt
HTR2ANM_000621.5 linkuse as main transcriptc.1354C>T p.His452Tyr missense_variant 4/4 ENST00000542664.4
HTR2ANM_001378924.1 linkuse as main transcriptc.1354C>T p.His452Tyr missense_variant 4/4
HTR2ANM_001165947.5 linkuse as main transcriptc.865C>T p.His289Tyr missense_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HTR2AENST00000542664.4 linkuse as main transcriptc.1354C>T p.His452Tyr missense_variant 4/41 NM_000621.5 P1P28223-1
HTR2AENST00000543956.5 linkuse as main transcriptc.865C>T p.His289Tyr missense_variant 3/31

Frequencies

GnomAD3 genomes
AF:
0.0931
AC:
14163
AN:
152046
Hom.:
717
Cov.:
32
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.:
33
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.:
32
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
T
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
N
MetaRNN
Benign
0.0016
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.55
N;N;.
MutationTaster
Benign
1.0
P;P;P
PrimateAI
Benign
0.27
T
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
T
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.

Other links and lift over

dbSNP: rs6314; hg19: chr13-47409034; COSMIC: COSV66327120; API