Variant chr13-46895833-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000621.5(HTR2A):c.74C>T(p.Thr25Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T25N) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

HTR2A
NM_000621.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.85

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.083485425).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
HTR2A	NM_000621.5 linkuse as main transcript	c.74C>T	p.Thr25Ile	missense_variant	2/4	ENST00000542664.4	NP_000612.1
HTR2A	NM_001378924.1 linkuse as main transcript	c.74C>T	p.Thr25Ile	missense_variant	2/4		NP_001365853.1
HTR2A	NM_001165947.5 linkuse as main transcript	c.-78+841C>T		intron_variant			NP_001159419.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HTR2A	ENST00000542664.4 linkuse as main transcript	c.74C>T	p.Thr25Ile	missense_variant	2/4	1	NM_000621.5	ENSP00000437737	P1	P28223-1
HTR2A	ENST00000543956.5 linkuse as main transcript	c.-78+841C>T		intron_variant		1		ENSP00000441861
HTR2A	ENST00000612998.1 linkuse as main transcript			upstream_gene_variant				ENSP00000482708

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461792

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.093

T;T

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.31

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.75

.;T

M_CAP

Benign

0.0098

MetaRNN

Benign

0.083

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.20

N;N

REVEL

Benign

0.018

Sift

Benign

0.059

T;T

Sift4G

Benign

0.41

T;T

Polyphen

0.037

B;B

Vest4

0.091

MutPred

0.22

Loss of phosphorylation at T25 (P = 0.0388);Loss of phosphorylation at T25 (P = 0.0388);

MVP

0.49

MPC

0.36

ClinPred

0.35

GERP RS

3.4

Varity_R

0.061

gMVP

0.54

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