dbSNP rs2246127: HTR2A:c.614-20705T>C (chr13-46856344-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.147

Publications

1 publications found

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:

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

HTR2A-AS1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_000621.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000621.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HTR2A	NM_000621.5	MANE Select	c.614-20705T>C	intron	N/A	NP_000612.1	P28223-1
HTR2A	NM_001378924.1		c.614-20705T>C	intron	N/A	NP_001365853.1	P28223-1
HTR2A	NM_001165947.5		c.125-20705T>C	intron	N/A	NP_001159419.2	A0A7P0PKG8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HTR2A	ENST00000542664.4	TSL:1 MANE Select	c.614-20705T>C	intron	N/A	ENSP00000437737.1	P28223-1
HTR2A	ENST00000543956.5	TSL:1	c.125-20705T>C	intron	N/A	ENSP00000441861.2	A0A7P0PKG8
HTR2A	ENST00000941626.1		c.614-20705T>C	intron	N/A	ENSP00000611685.1

Frequencies

GnomAD3 genomes

AF:

0.445

AC:

67522

AN:

151894

Hom.:

15694

Cov.:

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:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.445

AC:

67574

AN:

152012

Hom.:

15707

Cov.:

AF XY:

0.447

AC XY:

33216

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.565

AC:

23410

AN:

41466

American (AMR)

AF:

0.468

AC:

7151

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.369

AC:

1282

AN:

3470

East Asian (EAS)

AF:

0.367

AC:

1899

AN:

5168

South Asian (SAS)

AF:

0.459

AC:

2212

AN:

4820

European-Finnish (FIN)

AF:

0.441

AC:

4646

AN:

10546

Middle Eastern (MID)

AF:

0.353

AC:

103

AN:

292

European-Non Finnish (NFE)

AF:

0.377

AC:

25590

AN:

67956

Other (OTH)

AF:

0.416

AC:

875

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1863

3725

5588

7450

9313

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

620

1240

1860

2480

3100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.403

Hom.:

17246

Bravo

AF:

0.450

Asia WGS

AF:

0.437

AC:

1521

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

3.7

(source)

DANN

Benign

0.90

PhyloP100

-0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over