dbSNP rs2296973: HTR2A:c.413-56A>C (chr13-46892646-T-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.413-56A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 1,410,948 control chromosomes in the GnomAD database, including 354,615 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 0.73 ( 40460 hom., cov: 32)

Exomes 𝑓: 0.71 ( 314155 hom. )

Consequence

HTR2A
NM_000621.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.91

Publications

13 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:

Genome browser will be placed here

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 (AFR) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HTR2A	NM_000621.5 link	c.413-56A>C	intron_variant	Intron 2 of 3	ENST00000542664.4	NP_000612.1	P28223-1
HTR2A	NM_001378924.1 link	c.413-56A>C	intron_variant	Intron 2 of 3		NP_001365853.1
HTR2A	NM_001165947.5 link	c.-77-56A>C	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.413-56A>C		intron_variant	Intron 2 of 3	1	NM_000621.5	ENSP00000437737.1		P28223-1

Frequencies

GnomAD3 genomes

AF:

0.728

AC:

110658

AN:

151988

Hom.:

40419

Cov.:

show subpopulations

Gnomad AFR

AF:

0.792

Gnomad AMI

AF:

0.716

Gnomad AMR

AF:

0.706

Gnomad ASJ

AF:

0.765

Gnomad EAS

AF:

0.660

Gnomad SAS

AF:

0.657

Gnomad FIN

AF:

0.669

Gnomad MID

AF:

0.747

Gnomad NFE

AF:

0.711

Gnomad OTH

AF:

0.736

GnomAD4 exome

AF:

0.706

AC:

888148

AN:

1258842

Hom.:

314155

AF XY:

0.705

AC XY:

448810

AN XY:

636246

show subpopulations

African (AFR)

AF:

0.793

AC:

23409

AN:

29512

American (AMR)

AF:

0.648

AC:

28506

AN:

43962

Ashkenazi Jewish (ASJ)

AF:

0.765

AC:

18855

AN:

24660

East Asian (EAS)

AF:

0.624

AC:

24161

AN:

38716

South Asian (SAS)

AF:

0.663

AC:

54506

AN:

82182

European-Finnish (FIN)

AF:

0.661

AC:

34977

AN:

52884

Middle Eastern (MID)

AF:

0.746

AC:

3142

AN:

4210

European-Non Finnish (NFE)

AF:

0.713

AC:

662437

AN:

929144

Other (OTH)

AF:

0.712

AC:

38155

AN:

53572

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

13357

26714

40072

53429

66786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15476

30952

46428

61904

77380

<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:

0.728

AC:

110755

AN:

152106

Hom.:

40460

Cov.:

AF XY:

0.724

AC XY:

53855

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.792

AC:

32869

AN:

41492

American (AMR)

AF:

0.706

AC:

10791

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.765

AC:

2657

AN:

3472

East Asian (EAS)

AF:

0.660

AC:

3416

AN:

5176

South Asian (SAS)

AF:

0.657

AC:

3165

AN:

4814

European-Finnish (FIN)

AF:

0.669

AC:

7075

AN:

10572

Middle Eastern (MID)

AF:

0.741

AC:

218

AN:

294

European-Non Finnish (NFE)

AF:

0.711

AC:

48351

AN:

67968

Other (OTH)

AF:

0.737

AC:

1560

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1543

3086

4629

6172

7715

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

836

1672

2508

3344

4180

<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:

0.713

Hom.:

30759

Bravo

AF:

0.731

Asia WGS

AF:

0.682

AC:

2371

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

1.1

(source)

DANN

Benign

0.36

PhyloP100

-1.9

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