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GeneBe

13-46835596-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_000621.5(HTR2A):c.657G>A(p.Ser219=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,613,904 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00093 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0013 ( 0 hom. )

Consequence

HTR2A
NM_000621.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.00
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 13-46835596-C-T is Benign according to our data. Variant chr13-46835596-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 712185.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr13-46835596-C-T is described in Lovd as [Likely_benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 142 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HTR2ANM_000621.5 linkuse as main transcriptc.657G>A p.Ser219= synonymous_variant 4/4 ENST00000542664.4
HTR2ANM_001378924.1 linkuse as main transcriptc.657G>A p.Ser219= synonymous_variant 4/4
HTR2ANM_001165947.5 linkuse as main transcriptc.168G>A p.Ser56= synonymous_variant 3/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HTR2AENST00000542664.4 linkuse as main transcriptc.657G>A p.Ser219= synonymous_variant 4/41 NM_000621.5 P1P28223-1
HTR2AENST00000543956.5 linkuse as main transcriptc.168G>A p.Ser56= synonymous_variant 3/31

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000933
AC:
142
AN:
152124
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000434
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00293
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00129
Gnomad OTH
AF:
0.000955
GnomAD3 exomes
AF:
0.00106
AC:
265
AN:
250820
Hom.:
0
AF XY:
0.000996
AC XY:
135
AN XY:
135570
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.0000869
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00259
Gnomad NFE exome
AF:
0.00166
Gnomad OTH exome
AF:
0.00131
GnomAD4 exome
AF:
0.00129
AC:
1889
AN:
1461662
Hom.:
0
Cov.:
33
AF XY:
0.00125
AC XY:
906
AN XY:
727128
show subpopulations
Gnomad4 AFR exome
AF:
0.000209
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.000174
Gnomad4 FIN exome
AF:
0.00268
Gnomad4 NFE exome
AF:
0.00148
Gnomad4 OTH exome
AF:
0.00103
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000933
AC:
142
AN:
152242
Hom.:
1
Cov.:
32
AF XY:
0.000846
AC XY:
63
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.000433
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00293
Gnomad4 NFE
AF:
0.00129
Gnomad4 OTH
AF:
0.000945
Alfa
AF:
0.00110
Hom.:
0
Bravo
AF:
0.000706
EpiCase
AF:
0.00120
EpiControl
AF:
0.000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJul 21, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.33
Cadd
Benign
6.3
Dann
Benign
0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs35480504; hg19: chr13-47409731; COSMIC: COSV101096822; API