rs12662510

Positions:

• chr6-55215093-A-G
• chr6-55215093-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384272.1(HCRTR2):​c.224-33546A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,166 control chromosomes in the GnomAD database, including 1,834 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 0.14 (1834 hom., cov: 32)
• Consequence: HCRTR2 NM_001384272.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.831

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HCRTR2	NM_001384272.1	c.224-33546A>G		intron_variant		ENST00000370862.4	NP_001371201.1
HCRTR2	NM_001526.5	c.224-33546A>G		intron_variant			NP_001517.2
HCRTR2	XM_017010798.2	c.224-33546A>G		intron_variant			XP_016866287.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HCRTR2	ENST00000370862.4	c.224-33546A>G		intron_variant		1	NM_001384272.1	ENSP00000359899.3
HCRTR2	ENST00000615358.4	c.224-33546A>G		intron_variant		1		ENSP00000477548.1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20695 AN: 152048 Hom.: 1830 Cov.: 32

Gnomad AFR AF: 0.0429

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.162

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.136 AC: 20707 AN: 152166 Hom.: 1834 Cov.: 32 AF XY: 0.139 AC XY: 10329 AN XY: 74402

Gnomad4 AFR AF: 0.0428

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.160

Alfa AF: 0.153 Hom.: 357

Bravo AF: 0.144

Asia WGS AF: 0.189 AC: 658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.67

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

Other links and lift over

dbSNP: rs12662510; hg19: chr6-55079891;