Variant 17-81810907-CT-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_000160.5(GCGR):c.247delT(p.Trp83fs) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000478 in 1,526,740 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

GCGR
NM_000160.5 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 4.53

Variant links:

Genes affected

GCGR (HGNC:4192): (glucagon receptor) The protein encoded by this gene is a glucagon receptor that is important in controlling blood glucose levels. Defects in this gene are a cause of non-insulin-dependent diabetes mellitus (NIDDM).[provided by RefSeq, Jan 2010]

GCGR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 17-81810907-CT-C is Pathogenic according to our data. Variant chr17-81810907-CT-C is described in ClinVar as [Pathogenic]. Clinvar id is 2582843.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCGR	NM_000160.5 link	c.247delT	p.Trp83fs	frameshift_variant	4/14	ENST00000400723.8	NP_000151.1	P47871
GCGR	XM_006722277.2 link	c.247delT	p.Trp83fs	frameshift_variant	4/14		XP_006722340.1	P47871
GCGR	XM_017024446.2 link	c.241delT	p.Trp81fs	frameshift_variant	4/14		XP_016879935.1
GCGR	XM_011523539.2 link	c.171delT	p.Val58fs	frameshift_variant, splice_region_variant	2/12		XP_011521841.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GCGR	ENST00000400723.8 link	c.247delT	p.Trp83fs	frameshift_variant	4/14	1	NM_000160.5	ENSP00000383558.3	P47871
GCGR	ENST00000570996.5 link	c.247delT	p.Trp83fs	frameshift_variant	4/12	2		ENSP00000460976.1	I3L454
GCGR	ENST00000574283.2 link	n.331delT		non_coding_transcript_exon_variant	2/3	5
GCGR	ENST00000573428.1 link	c.*7delT		downstream_gene_variant		4		ENSP00000458930.1	I3L1L8

Frequencies

GnomAD3 genomes

AF:

0.0000200

AC:

AN:

150084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000445

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000508

AC:

AN:

1376656

Hom.:

Cov.:

AF XY:

0.0000368

AC XY:

AN XY:

679228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000587

Gnomad4 OTH exome

AF:

0.000122

GnomAD4 genome

AF:

0.0000200

AC:

AN:

150084

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73292

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000445

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

GCGR-related hyperglucagonemia

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Ganetzky Laboratory, Children's Hospital of Philadelphia

Jun 29, 2023

PVS1+PM2+PM3+PP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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