rs2246127

Variant summary

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

The NM_000621.5(HTR2A):​c.614-20705T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 152,012 control chromosomes in the GnomAD database, including 15,707 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.

Frequency

Genomes: 𝑓 0.44 ( 15707 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

HTR2A
NM_000621.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.147
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-AS1 (HGNC:40289): (HTR2A antisense RNA 1)

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 (BayesDel_noAF=-0.71).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HTR2ANM_000621.5 linkuse as main transcriptc.614-20705T>C intron_variant ENST00000542664.4
HTR2A-AS1NR_046612.1 linkuse as main transcript downstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HTR2AENST00000542664.4 linkuse as main transcriptc.614-20705T>C intron_variant 1 NM_000621.5 P1P28223-1
HTR2AENST00000543956.5 linkuse as main transcriptc.125-20705T>C intron_variant 1
HTR2A-AS1ENST00000455126.5 linkuse as main transcript downstream_gene_variant 5
HTR2A-AS1ENST00000430913.2 linkuse as main transcript downstream_gene_variant 3

Frequencies

GnomAD3 genomes
AF:
0.445
AC:
67522
AN:
151894
Hom.:
15694
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.565
Gnomad AMI
AF:
0.445
Gnomad AMR
AF:
0.468
Gnomad ASJ
AF:
0.369
Gnomad EAS
AF:
0.367
Gnomad SAS
AF:
0.460
Gnomad FIN
AF:
0.441
Gnomad MID
AF:
0.354
Gnomad NFE
AF:
0.377
Gnomad OTH
AF:
0.415
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
2
Hom.:
0
Cov.:
0
AC XY:
0
AN XY:
0
Gnomad4 FIN exome
AF:
0.00
GnomAD4 genome
AF:
0.445
AC:
67574
AN:
152012
Hom.:
15707
Cov.:
32
AF XY:
0.447
AC XY:
33216
AN XY:
74302
show subpopulations
Gnomad4 AFR
AF:
0.565
Gnomad4 AMR
AF:
0.468
Gnomad4 ASJ
AF:
0.369
Gnomad4 EAS
AF:
0.367
Gnomad4 SAS
AF:
0.459
Gnomad4 FIN
AF:
0.441
Gnomad4 NFE
AF:
0.377
Gnomad4 OTH
AF:
0.416
Alfa
AF:
0.411
Hom.:
2751
Bravo
AF:
0.450
Asia WGS
AF:
0.437
AC:
1521
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.71
CADD
Benign
3.7
DANN
Benign
0.90

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: rs2246127; hg19: chr13-47430479; API