Genetic Variant HTR2A:c.-311G>A (chr13-46896217-C-T) – 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.-311G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.938 in 1,125,922 control chromosomes in the GnomAD database, including 495,678 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 0.91 ( 62927 hom., cov: 32)

Exomes 𝑓: 0.94 ( 432751 hom. )

Consequence

HTR2A
NM_000621.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.25

Publications

12 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:

ENSG00000301465 (HGNC:):

ENSG00000301465 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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HTR2A	NM_000621.5 link	c.-311G>A	5_prime_UTR_variant	Exon 2 of 4	ENST00000542664.4	NP_000612.1	P28223-1
HTR2A	NM_001378924.1 link	c.-311G>A	5_prime_UTR_variant	Exon 2 of 4		NP_001365853.1
HTR2A	NM_001165947.5 link	c.-78+457G>A	intron_variant	Intron 1 of 2		NP_001159419.2	P28223

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR2A	ENST00000542664.4 link	c.-311G>A		5_prime_UTR_variant	Exon 2 of 4	1	NM_000621.5	ENSP00000437737.1		P28223-1

Frequencies

GnomAD3 genomes

AF:

0.907

AC:

137965

AN:

152056

Hom.:

62888

Cov.:

show subpopulations

Gnomad AFR

AF:

0.805

Gnomad AMI

AF:

0.945

Gnomad AMR

AF:

0.943

Gnomad ASJ

AF:

0.905

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.927

Gnomad FIN

AF:

0.951

Gnomad MID

AF:

0.930

Gnomad NFE

AF:

0.945

Gnomad OTH

AF:

0.915

GnomAD4 exome

AF:

0.942

AC:

917676

AN:

973748

Hom.:

432751

Cov.:

AF XY:

0.942

AC XY:

429572

AN XY:

455808

show subpopulations

African (AFR)

AF:

0.791

AC:

15877

AN:

20078

American (AMR)

AF:

0.951

AC:

6748

AN:

7092

Ashkenazi Jewish (ASJ)

AF:

0.899

AC:

9354

AN:

10402

East Asian (EAS)

AF:

1.00

AC:

13757

AN:

13758

South Asian (SAS)

AF:

0.930

AC:

20191

AN:

21702

European-Finnish (FIN)

AF:

0.950

AC:

7752

AN:

8156

Middle Eastern (MID)

AF:

0.886

AC:

2071

AN:

2338

European-Non Finnish (NFE)

AF:

0.946

AC:

807764

AN:

853440

Other (OTH)

AF:

0.929

AC:

34162

AN:

36782

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

2323

4646

6969

9292

11615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20568

41136

61704

82272

102840

<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:

0.907

AC:

138058

AN:

152174

Hom.:

62927

Cov.:

AF XY:

0.909

AC XY:

67665

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.805

AC:

33385

AN:

41466

American (AMR)

AF:

0.944

AC:

14432

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.905

AC:

3141

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5175

AN:

5178

South Asian (SAS)

AF:

0.926

AC:

4462

AN:

4816

European-Finnish (FIN)

AF:

0.951

AC:

10085

AN:

10602

Middle Eastern (MID)

AF:

0.929

AC:

273

AN:

294

European-Non Finnish (NFE)

AF:

0.945

AC:

64312

AN:

68032

Other (OTH)

AF:

0.916

AC:

1933

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

639

1278

1916

2555

3194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

902

1804

2706

3608

4510

<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:

0.885

Hom.:

5531

Bravo

AF:

0.902

Asia WGS

AF:

0.957

AC:

3327

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.9

(source)

DANN

Benign

0.61

PhyloP100

1.3

PromoterAI

0.018

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

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