11-119107769-G-T

Position:

chr11-119107769-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001290474.2(C2CD2L):c.28G>T(p.Val10Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000338 in 1,540,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

C2CD2L
NM_001290474.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.95

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022919595).

BS2

High AC in GnomAd4 at 31 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C2CD2L	NM_001290474.2 link	c.28G>T	p.Val10Leu	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.28G>T	p.Val10Leu	missense_variant	1/14		NM_001290474.2	ENSP00000497391.1	O14523-1
C2CD2L	ENST00000336702.7 link	c.28G>T	p.Val10Leu	missense_variant	1/14	1		ENSP00000338885.3	O14523-2
DPAGT1	ENST00000409993.6 link	c.-990C>A		5_prime_UTR_variant	1/11	2		ENSP00000386597.2	Q9H3H5-1
C2CD2L	ENST00000527854.1 link	n.*11G>T		downstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

151924

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000666

AC:

AN:

165044

Hom.:

AF XY:

0.0000318

AC XY:

AN XY:

94378

show subpopulations

Gnomad AFR exome

AF:

0.00130

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.000261

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1388122

Hom.:

Cov.:

AF XY:

0.0000145

AC XY:

AN XY:

690616

show subpopulations

Gnomad4 AFR exome

AF:

0.000490

Gnomad4 AMR exome

AF:

0.0000568

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000696

GnomAD4 genome

AF:

0.000204

AC:

AN:

152030

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.000723

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000201

Hom.:

Bravo

AF:

0.000223

ESP6500AA

AF:

0.000954

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000102

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 19, 2024

The c.28G>T (p.V10L) alteration is located in exon 1 (coding exon 1) of the C2CD2L gene. This alteration results from a G to T substitution at nucleotide position 28, causing the valine (V) at amino acid position 10 to be replaced by a leucine (L). 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

0.096

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.0081

.;T

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.017

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.66

T;T

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.023

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.38

N;N

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.43

N;.

REVEL

Benign

0.016

Sift

Benign

0.26

T;.

Sift4G

Benign

0.64

T;.

Polyphen

0.049

B;B

Vest4

0.12

MutPred

0.23

Gain of disorder (P = 0.2064);Gain of disorder (P = 0.2064);

MVP

0.043

MPC

0.47

ClinPred

0.082

GERP RS

4.4

Varity_R

0.11

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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