Genetic Variant HTR2A:c.614-2211T>C (chr13-46837850-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is . The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000621.5(HTR2A):c.614-2211T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 152,198 control chromosomes in the GnomAD database, including 37,960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.69 ( 37960 hom., cov: 34)

Consequence

HTR2A
NM_000621.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 1.48

Publications

152 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:

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 13-46837850-A-G is Benign according to our data. Variant chr13-46837850-A-G is described in ClinVar as Benign. ClinVar VariationId is 226025.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.919 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.614-2211T>C	intron	N/A	NP_000612.1	P28223-1
HTR2A	NM_001378924.1		c.614-2211T>C	intron	N/A	NP_001365853.1	P28223-1
HTR2A	NM_001165947.5		c.125-2211T>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.614-2211T>C	intron	N/A	ENSP00000437737.1	P28223-1
HTR2A	ENST00000543956.5	TSL:1	c.125-2211T>C	intron	N/A	ENSP00000441861.2	A0A7P0PKG8
HTR2A	ENST00000941626.1		c.614-2211T>C	intron	N/A	ENSP00000611685.1

Frequencies

GnomAD3 genomes

AF:

0.686

AC:

104370

AN:

152080

Hom.:

37922

Cov.:

show subpopulations

Gnomad AFR

AF:

0.927

Gnomad AMI

AF:

0.620

Gnomad AMR

AF:

0.686

Gnomad ASJ

AF:

0.719

Gnomad EAS

AF:

0.741

Gnomad SAS

AF:

0.593

Gnomad FIN

AF:

0.447

Gnomad MID

AF:

0.693

Gnomad NFE

AF:

0.578

Gnomad OTH

AF:

0.695

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.686

AC:

104464

AN:

152198

Hom.:

37960

Cov.:

AF XY:

0.680

AC XY:

50595

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.927

AC:

38513

AN:

41558

American (AMR)

AF:

0.686

AC:

10495

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.719

AC:

2496

AN:

3472

East Asian (EAS)

AF:

0.740

AC:

3825

AN:

5168

South Asian (SAS)

AF:

0.591

AC:

2852

AN:

4826

European-Finnish (FIN)

AF:

0.447

AC:

4733

AN:

10582

Middle Eastern (MID)

AF:

0.687

AC:

202

AN:

294

European-Non Finnish (NFE)

AF:

0.578

AC:

39323

AN:

67982

Other (OTH)

AF:

0.692

AC:

1460

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1536

3072

4607

6143

7679

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

794

1588

2382

3176

3970

<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:

0.625

Hom.:

62942

Bravo

AF:

0.719

Asia WGS

AF:

0.671

AC:

2336

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Major depressive disorder, response to citalopram therapy in (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

1.5

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