17-81810875-C-G

Position:

• chr17-81810875-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000160.5(GCGR):​c.214C>G​(p.Pro72Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GCGR NM_000160.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.36

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08276802).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GCGR	NM_000160.5	c.214C>G	p.Pro72Ala	missense_variant	4/14	ENST00000400723.8	NP_000151.1
GCGR	XM_006722277.2	c.214C>G	p.Pro72Ala	missense_variant	4/14		XP_006722340.1
GCGR	XM_017024446.2	c.208C>G	p.Pro70Ala	missense_variant	4/14		XP_016879935.1
GCGR	XM_011523539.2	c.138C>G	p.Pro46Pro	synonymous_variant	2/12		XP_011521841.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GCGR	ENST00000400723.8	c.214C>G	p.Pro72Ala	missense_variant	4/14	1	NM_000160.5	ENSP00000383558.3
GCGR	ENST00000570996.5	c.214C>G	p.Pro72Ala	missense_variant	4/12	2		ENSP00000460976.1
GCGR	ENST00000573428.1	c.214C>G	p.Pro72Ala	missense_variant	4/4	4		ENSP00000458930.1
GCGR	ENST00000574283.2	n.298C>G		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 43

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 06, 2023

The c.214C>G (p.P72A) alteration is located in exon 4 (coding exon 3) of the GCGR gene. This alteration results from a C to G substitution at nucleotide position 214, causing the proline (P) at amino acid position 72 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	5.0
DANN	Benign	0.19
DEOGEN2	Benign	0.086	T;.;.
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.41	T;T;T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.083	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.;.
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.060	N;.;.
REVEL	Benign	0.12
Sift	Benign	0.95	T;.;.
Sift4G	Benign	0.89	T;T;T
Polyphen		0.013	B;.;.
Vest4		0.28
MutPred		0.27		Loss of phosphorylation at T71 (P = 0.109);Loss of phosphorylation at T71 (P = 0.109);Loss of phosphorylation at T71 (P = 0.109);
MVP		0.69
MPC		0.0028
ClinPred		0.072	T
GERP RS		4.2
Varity_R		0.053
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-79768751;