Variant 17-9826128-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004246.3(GLP2R):c.65A>T(p.His22Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00367 in 1,612,796 control chromosomes in the GnomAD database, including 166 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.020 ( 82 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 84 hom. )

Consequence

GLP2R
NM_004246.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.857

Variant links:

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]

GLP2R links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023859143).

BP6

Variant 17-9826128-A-T is Benign according to our data. Variant chr17-9826128-A-T is described in ClinVar as [Benign]. Clinvar id is 781254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLP2R	NM_004246.3 link	c.65A>T	p.His22Leu	missense_variant	1/13	ENST00000262441.10	NP_004237.1	O95838A0A384MTS7B2RAN4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GLP2R	ENST00000262441.10 link	c.65A>T	p.His22Leu	missense_variant	1/13	1	NM_004246.3	ENSP00000262441.5	O95838
GLP2R	ENST00000574745.5 link	c.-352+3843A>T		intron_variant		2		ENSP00000458242.1	I3L0P5
GLP2R	ENST00000458005.2 link	n.65A>T		non_coding_transcript_exon_variant	1/11	5		ENSP00000404471.3	H0Y6C2

Frequencies

GnomAD3 genomes

AF:

0.0196

AC:

2988

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0684

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00727

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.00535

AC:

1323

AN:

247468

Hom.:

AF XY:

0.00385

AC XY:

515

AN XY:

133838

show subpopulations

Gnomad AFR exome

AF:

0.0708

Gnomad AMR exome

AF:

0.00450

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000266

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000125

Gnomad OTH exome

AF:

0.00248

GnomAD4 exome

AF:

0.00200

AC:

2920

AN:

1460524

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

1226

AN XY:

726442

show subpopulations

Gnomad4 AFR exome

AF:

0.0700

Gnomad4 AMR exome

AF:

0.00456

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000280

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000567

Gnomad4 OTH exome

AF:

0.00433

GnomAD4 genome

AF:

0.0196

AC:

2991

AN:

152272

Hom.:

Cov.:

AF XY:

0.0189

AC XY:

1406

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0682

Gnomad4 AMR

AF:

0.00726

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.0151

Alfa

AF:

0.00297

Hom.:

Bravo

AF:

0.0225

ESP6500AA

AF:

0.0647

AC:

285

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00661

AC:

803

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 31, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.030

DANN

Benign

0.35

DEOGEN2

Benign

0.039

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.16

MetaRNN

Benign

0.0024

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.41

REVEL

Benign

0.038

Sift

Benign

0.18

Sift4G

Benign

0.29

Polyphen

0.0

Vest4

0.19

MVP

0.48

MPC

0.35

ClinPred

0.0062

GERP RS

-3.5

Varity_R

0.038

gMVP

0.24

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