17-9861198-G-A

Position:

• chr17-9861198-G-A

Variant summary

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

The NM_004246.3(GLP2R):​c.985G>A​(p.Gly329Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GLP2R NM_004246.3 missense, splice_region
• Scores: Splicing: ADA: 0.0003371
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.85

Genes affected

GLP2R (HGNC:4325): (glucagon like peptide 2 receptor) This gene encodes a G protein-coupled receptor that is closely related to the glucagon receptor and binds to glucagon-like peptide-2 (GLP2). Signalling through GLP2 stimulates intestinal growth and increases villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLP2R	NM_004246.3	c.985G>A	p.Gly329Arg	missense_variant, splice_region_variant	8/13	ENST00000262441.10	NP_004237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLP2R	ENST00000262441.10	c.985G>A	p.Gly329Arg	missense_variant, splice_region_variant	8/13	1	NM_004246.3	ENSP00000262441.5
GLP2R	ENST00000574745.5	c.445G>A	p.Gly149Arg	missense_variant, splice_region_variant	8/13	2		ENSP00000458242.1
GLP2R	ENST00000458005.2	n.*949G>A		splice_region_variant, non_coding_transcript_exon_variant	9/11	5		ENSP00000404471.3
GLP2R	ENST00000458005.2	n.*949G>A		3_prime_UTR_variant	9/11	5		ENSP00000404471.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000756

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 23, 2023

The c.985G>A (p.G329R) alteration is located in exon 8 (coding exon 8) of the GLP2R gene. This alteration results from a G to A substitution at nucleotide position 985, causing the glycine (G) at amino acid position 329 to be replaced by an arginine (R). 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	0.27
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	23
DANN	Benign	0.78
DEOGEN2	Benign	0.068	.;T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.72	T;T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.44	T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.1	.;N
REVEL	Benign	0.13
Sift	Benign	0.17	.;T
Sift4G	Benign	0.27	T;T
Polyphen		0.049	.;B
Vest4		0.38
MutPred		0.85		.;Gain of MoRF binding (P = 0.0127);
MVP		0.65
MPC		0.84
ClinPred		0.90	D
GERP RS		3.2
Varity_R		0.079
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00034
dbscSNV1_RF	Benign	0.10
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: rs1482651626; hg19: chr17-9764515;