17-9857575-A-C

Position:

• chr17-9857575-A-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_004246.3(GLP2R):​c.764A>C​(p.Glu255Ala) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00156 in 1,614,058 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0088 (22 hom., cov: 33)
  • Exomes 𝑓: 0.00081 (20 hom.)
• Consequence: GLP2R NM_004246.3 missense, splice_region
• Scores: Splicing: ADA: 0.9957
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.37

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 Benign. Variant got -16 ACMG points.

• BP6: Variant 17-9857575-A-C is Benign according to our data. Variant chr17-9857575-A-C is described in ClinVar as [Benign]. Clinvar id is 790177.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00875 (1333/152288) while in subpopulation AFR AF= 0.0302 (1256/41566). AF 95% confidence interval is 0.0288. There are 22 homozygotes in gnomad4. There are 619 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLP2R	NM_004246.3	c.764A>C	p.Glu255Ala	missense_variant, splice_region_variant	6/13	ENST00000262441.10	NP_004237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLP2R	ENST00000262441.10	c.764A>C	p.Glu255Ala	missense_variant, splice_region_variant	6/13	1	NM_004246.3	ENSP00000262441.5

Frequencies

GnomAD3 genomes AF: 0.00874 AC: 1330 AN: 152170 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.0302

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00334

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.00220 AC: 554 AN: 251432 Hom.: 7 AF XY: 0.00166 AC XY: 225 AN XY: 135884

Gnomad AFR exome AF: 0.0311

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000615

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000814 AC: 1190 AN: 1461770 Hom.: 20 Cov.: 31 AF XY: 0.000699 AC XY: 508 AN XY: 727196

Gnomad4 AFR exome AF: 0.0295

Gnomad4 AMR exome AF: 0.00119

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000216

Gnomad4 OTH exome AF: 0.00182

GnomAD4 genome AF: 0.00875 AC: 1333 AN: 152288 Hom.: 22 Cov.: 33 AF XY: 0.00831 AC XY: 619 AN XY: 74466

Gnomad4 AFR AF: 0.0302

Gnomad4 AMR AF: 0.00333

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.00193 Hom.: 8

Bravo AF: 0.0101

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0279 AC: 123

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00273 AC: 332

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 13, 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	0.14
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	28
DANN	Benign	0.83
DEOGEN2	Benign	0.21	.;T;.
Eigen	Benign	0.075
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.70	T;T;T
MetaRNN	Benign	0.0051	T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.8	.;L;.
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-3.2	.;D;.
REVEL	Benign	0.18
Sift	Benign	0.23	.;T;.
Sift4G	Benign	0.39	T;T;T
Polyphen		0.24	.;B;.
Vest4		0.32
MVP		0.88
MPC		0.74
ClinPred		0.051	T
GERP RS		5.3
Varity_R		0.15
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.77
SpliceAI score (max)		0.65		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.65		Position offset: 46

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs61730821; hg19: chr17-9760892;