Variant 6-55277463-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001384272.1(HCRTR2):c.846G>A(p.Thr282=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00511 in 1,614,052 control chromosomes in the GnomAD database, including 333 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 194 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 139 hom. )

Consequence

HCRTR2
NM_001384272.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0150

Variant links:

Genes affected

HCRTR2 (HGNC:4849): (hypocretin receptor 2) The protein encoded by this gene is a G-protein coupled receptor involved in the regulation of feeding behavior. The encoded protein binds the hypothalamic neuropeptides orexin A and orexin B. A related gene (HCRTR1) encodes a G-protein coupled receptor that selectively binds orexin A. [provided by RefSeq, Jan 2009]

HCRTR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 6-55277463-G-A is Benign according to our data. Variant chr6-55277463-G-A is described in ClinVar as [Benign]. Clinvar id is 768101.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.015 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.085 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HCRTR2	NM_001384272.1 linkuse as main transcript	c.846G>A	p.Thr282=	synonymous_variant	5/7	ENST00000370862.4
HCRTR2	NM_001526.5 linkuse as main transcript	c.846G>A	p.Thr282=	synonymous_variant	6/8
HCRTR2	XM_017010798.2 linkuse as main transcript	c.846G>A	p.Thr282=	synonymous_variant	6/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCRTR2	ENST00000370862.4 linkuse as main transcript	c.846G>A	p.Thr282=	synonymous_variant	5/7	1	NM_001384272.1	P1
HCRTR2	ENST00000615358.4 linkuse as main transcript	c.846G>A	p.Thr282=	synonymous_variant	6/8	1		P1

Frequencies

GnomAD3 genomes

AF:

0.0255

AC:

3885

AN:

152154

Hom.:

193

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0872

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.00731

AC:

1834

AN:

251058

Hom.:

AF XY:

0.00549

AC XY:

745

AN XY:

135670

show subpopulations

Gnomad AFR exome

AF:

0.0881

Gnomad AMR exome

AF:

0.00675

Gnomad ASJ exome

AF:

0.00318

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000751

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000722

Gnomad OTH exome

AF:

0.00474

GnomAD4 exome

AF:

0.00297

AC:

4341

AN:

1461780

Hom.:

139

Cov.:

AF XY:

0.00268

AC XY:

1950

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.0861

Gnomad4 AMR exome

AF:

0.00696

Gnomad4 ASJ exome

AF:

0.00291

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000707

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000487

Gnomad4 OTH exome

AF:

0.00686

GnomAD4 genome

AF:

0.0256

AC:

3903

AN:

152272

Hom.:

194

Cov.:

AF XY:

0.0251

AC XY:

1866

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0874

Gnomad4 AMR

AF:

0.0109

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000573

Gnomad4 OTH

AF:

0.0218

Alfa

AF:

0.00762

Hom.:

Bravo

AF:

0.0292

Asia WGS

AF:

0.00578

AC:

AN:

3476

EpiCase

AF:

0.000655

EpiControl

AF:

0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

HCRTR2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 31, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

5.0

DANN

Benign

0.54

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over