dbSNP rs2296972: HTR2A:c.614-18697T>G (chr13-46854336-A-C) – 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.614-18697T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 152,146 control chromosomes in the GnomAD database, including 36,831 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 0.69 ( 36828 hom., cov: 33)

Exomes 𝑓: 0.88 ( 3 hom. )

Consequence

HTR2A
NM_000621.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.813

Publications

32 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:

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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=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR2A	NM_000621.5 link	c.614-18697T>G		intron_variant	Intron 3 of 3	ENST00000542664.4	NP_000612.1	P28223-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR2A	ENST00000542664.4 link	c.614-18697T>G		intron_variant	Intron 3 of 3	1	NM_000621.5	ENSP00000437737.1		P28223-1

Frequencies

GnomAD3 genomes

AF:

0.692

AC:

105227

AN:

152020

Hom.:

36814

Cov.:

show subpopulations

Gnomad AFR

AF:

0.767

Gnomad AMI

AF:

0.632

Gnomad AMR

AF:

0.602

Gnomad ASJ

AF:

0.684

Gnomad EAS

AF:

0.472

Gnomad SAS

AF:

0.513

Gnomad FIN

AF:

0.646

Gnomad MID

AF:

0.696

Gnomad NFE

AF:

0.705

Gnomad OTH

AF:

0.690

GnomAD4 exome

AF:

0.875

AC:

AN:

Hom.:

AF XY:

0.833

AC XY:

AN XY:

show subpopulations

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)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.833

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.692

AC:

105271

AN:

152138

Hom.:

36828

Cov.:

AF XY:

0.681

AC XY:

50645

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.767

AC:

31845

AN:

41528

American (AMR)

AF:

0.601

AC:

9181

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.684

AC:

2372

AN:

3468

East Asian (EAS)

AF:

0.471

AC:

2440

AN:

5182

South Asian (SAS)

AF:

0.511

AC:

2459

AN:

4814

European-Finnish (FIN)

AF:

0.646

AC:

6827

AN:

10572

Middle Eastern (MID)

AF:

0.694

AC:

204

AN:

294

European-Non Finnish (NFE)

AF:

0.705

AC:

47926

AN:

67986

Other (OTH)

AF:

0.685

AC:

1441

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1653

3306

4960

6613

8266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

824

1648

2472

3296

4120

<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:

0.690

Hom.:

28503

Bravo

AF:

0.696

Asia WGS

AF:

0.517

AC:

1796

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.34

(source)

DANN

Benign

0.69

PhyloP100

-0.81

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over