Variant 11-119108075-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001290474.2(C2CD2L):c.334G>A(p.Glu112Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,596,974 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 2 hom., cov: 30)

Exomes 𝑓: 0.0014 ( 6 hom. )

Consequence

C2CD2L
NM_001290474.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.55

Variant links:

Genes affected

C2CD2L (HGNC:29000): (C2CD2 like) Enables phosphatidylinositol binding activity and phosphatidylinositol transfer activity. Involved in positive regulation of insulin secretion involved in cellular response to glucose stimulus. Located in cortical endoplasmic reticulum and endoplasmic reticulum-plasma membrane contact site. Colocalizes with cytoplasmic side of apical plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

C2CD2L links:

DPAGT1 (HGNC:2995): (dolichyl-phosphate N-acetylglucosaminephosphotransferase 1) The protein encoded by this gene is an enzyme that catalyzes the first step in the dolichol-linked oligosaccharide pathway for glycoprotein biosynthesis. This enzyme belongs to the glycosyltransferase family 4. This protein is an integral membrane protein of the endoplasmic reticulum. The congenital disorder of glycosylation type Ij is caused by mutation in the gene encoding this enzyme. [provided by RefSeq, Jul 2008]

DPAGT1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009098738).

BP6

Variant 11-119108075-G-A is Benign according to our data. Variant chr11-119108075-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2642457.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 233 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C2CD2L	NM_001290474.2 link	c.334G>A	p.Glu112Lys	missense_variant	1/14	ENST00000648610.2	NP_001277403.1	O14523-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
C2CD2L	ENST00000648610.2 link	c.334G>A	p.Glu112Lys	missense_variant	1/14		NM_001290474.2	ENSP00000497391.1	O14523-1
C2CD2L	ENST00000336702.7 link	c.334G>A	p.Glu112Lys	missense_variant	1/14	1		ENSP00000338885.3	O14523-2
DPAGT1	ENST00000409993.6 link	c.-1296C>T		5_prime_UTR_premature_start_codon_gain_variant	1/11	2		ENSP00000386597.2	Q9H3H5-1
DPAGT1	ENST00000409993.6 link	c.-1296C>T		5_prime_UTR_variant	1/11	2		ENSP00000386597.2	Q9H3H5-1

Frequencies

GnomAD3 genomes

AF:

0.00153

AC:

233

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00601

Gnomad FIN

AF:

0.00349

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00206

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00198

AC:

435

AN:

219450

Hom.:

AF XY:

0.00239

AC XY:

291

AN XY:

121818

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000335

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00529

Gnomad FIN exome

AF:

0.00374

Gnomad NFE exome

AF:

0.00185

Gnomad OTH exome

AF:

0.00207

GnomAD4 exome

AF:

0.00142

AC:

2055

AN:

1444774

Hom.:

Cov.:

AF XY:

0.00166

AC XY:

1193

AN XY:

719096

show subpopulations

Gnomad4 AFR exome

AF:

0.000193

Gnomad4 AMR exome

AF:

0.000369

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000272

Gnomad4 SAS exome

AF:

0.00545

Gnomad4 FIN exome

AF:

0.00380

Gnomad4 NFE exome

AF:

0.00110

Gnomad4 OTH exome

AF:

0.00157

GnomAD4 genome

AF:

0.00153

AC:

233

AN:

152200

Hom.:

Cov.:

AF XY:

0.00161

AC XY:

120

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00601

Gnomad4 FIN

AF:

0.00349

Gnomad4 NFE

AF:

0.00206

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00176

Hom.:

Bravo

AF:

0.000918

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000954

AC:

ExAC

AF:

0.00201

AC:

240

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2022

DPAGT1: BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.074

.;T

Eigen

Benign

0.024

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.0091

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

M;M

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.9

N;.

REVEL

Benign

0.053

Sift

Benign

0.061

T;.

Sift4G

Benign

0.080

T;.

Polyphen

0.49

P;P

Vest4

0.52

MVP

0.068

MPC

1.2

ClinPred

0.066

GERP RS

2.9

Varity_R

0.28

gMVP

0.49

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