13-102789089-T-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_024089.3(POGLUT2):c.1216A>C(p.Lys406Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

POGLUT2
NM_024089.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.92

Publications

1 publications found

Variant links:

Genes affected

POGLUT2 (HGNC:19350): (protein O-glucosyltransferase 2) This gene encodes a protein product localized to the lumen of the endoplasmic reticulum. As a member of the endoplasmic reticulum protein family the encoded protein contains a Lys-Asp-Glu-Leu or KDEL motif located at the extreme C-terminus which prevents all endoplasmic reticulum resident proteins from being secreted. Proteins carrying this motif are bound by a receptor in the Golgi apparatus so that the receptor-ligand complex returns to the endoplasmic reticulum. A processed non-transcribed pseudogene located in an intron of a sodium transporter gene on chromosome 5 has been defined for this gene. This gene has multiple transcript variants which are predicted to encode distinct isoforms. [provided by RefSeq, Jan 2016]

POGLUT2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37351754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POGLUT2	NM_024089.3 link	c.1216A>C	p.Lys406Gln	missense_variant	Exon 7 of 10	ENST00000376004.5	NP_076994.2	Q6UW63
POGLUT2	NM_001439010.1 link	c.1216A>C	p.Lys406Gln	missense_variant	Exon 7 of 9		NP_001425939.1
POGLUT2	NM_001318732.2 link	c.559A>C	p.Lys187Gln	missense_variant	Exon 8 of 11		NP_001305661.1	Q6UW63
POGLUT2	XM_047430604.1 link	c.559A>C	p.Lys187Gln	missense_variant	Exon 5 of 8		XP_047286560.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POGLUT2	ENST00000376004.5 link	c.1216A>C	p.Lys406Gln	missense_variant	Exon 7 of 10	1	NM_024089.3	ENSP00000365172.4		Q6UW63

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000795

AC:

AN:

251456

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000927

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111998

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 19, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1216A>C (p.K406Q) alteration is located in exon 7 (coding exon 7) of the KDELC1 gene. This alteration results from a A to C substitution at nucleotide position 1216, causing the lysine (K) at amino acid position 406 to be replaced by a glutamine (Q). 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

0.081

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.016

Eigen

Benign

-0.030

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0060

MetaRNN

Benign

0.37

MetaSVM

Benign

-1.1

PhyloP100

1.9

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.6

REVEL

Benign

0.041

Sift

Benign

0.13

Sift4G

Benign

0.53

Polyphen

0.21

Vest4

0.50

MutPred

0.45

Loss of methylation at K406 (P = 0.0048);

MVP

0.26

MPC

0.23

ClinPred

0.53

GERP RS

4.6

Varity_R

0.16

gMVP

0.65

Mutation Taster

=78/22

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

13-102789089-T-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over