NM_004246.3:c.1285-90G>A

Variant names:

• chr17-9887842-G-A
• rs2240737
• NM_004246.3:c.1285-90G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004246.3(GLP2R):​c.1285-90G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 900,440 control chromosomes in the GnomAD database, including 12,895 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (2274 hom., cov: 32)
  • Exomes 𝑓: 0.15 (10621 hom.)
• Consequence: GLP2R NM_004246.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0460
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLP2R	NM_004246.3	c.1285-90G>A		intron_variant	Intron 11 of 12	ENST00000262441.10	NP_004237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLP2R	ENST00000262441.10	c.1285-90G>A		intron_variant	Intron 11 of 12	1	NM_004246.3	ENSP00000262441.5
GLP2R	ENST00000574745.5	c.745-90G>A		intron_variant	Intron 11 of 12	2		ENSP00000458242.1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24307 AN: 152042 Hom.: 2269 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.152 AC: 113658 AN: 748280 Hom.: 10621 AF XY: 0.154 AC XY: 61571 AN XY: 399934

African (AFR) AF: 0.199 AC: 3955 AN: 19856

American (AMR) AF: 0.313 AC: 13727 AN: 43836

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 4044 AN: 21672

East Asian (EAS) AF: 0.264 AC: 9640 AN: 36518

South Asian (SAS) AF: 0.244 AC: 17574 AN: 71922

European-Finnish (FIN) AF: 0.140 AC: 7440 AN: 53068

Middle Eastern (MID) AF: 0.206 AC: 907 AN: 4400

European-Non Finnish (NFE) AF: 0.110 AC: 50624 AN: 460070

Other (OTH) AF: 0.156 AC: 5747 AN: 36938

GnomAD4 genome AF: 0.160 AC: 24342 AN: 152160 Hom.: 2274 Cov.: 32 AF XY: 0.164 AC XY: 12187 AN XY: 74390

African (AFR) AF: 0.191 AC: 7940 AN: 41498

American (AMR) AF: 0.252 AC: 3856 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 659 AN: 3470

East Asian (EAS) AF: 0.267 AC: 1381 AN: 5164

South Asian (SAS) AF: 0.246 AC: 1187 AN: 4816

European-Finnish (FIN) AF: 0.135 AC: 1429 AN: 10598

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7349 AN: 68008

Other (OTH) AF: 0.171 AC: 361 AN: 2108

Alfa AF: 0.137 Hom.: 2274

Bravo AF: 0.171

Asia WGS AF: 0.285 AC: 991 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.9
DANN	Benign	0.65
PhyloP100		-0.046
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2240737; hg19: chr17-9791159; COSMIC: COSV52322818;