11-119107853-T-G

Position:

• chr11-119107853-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001290474.2(C2CD2L):​c.112T>G​(p.Trp38Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
• Consequence: C2CD2L NM_001290474.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.341

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]

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37371337).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C2CD2L	NM_001290474.2	c.112T>G	p.Trp38Gly	missense_variant	1/14	ENST00000648610.2	NP_001277403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C2CD2L	ENST00000648610.2	c.112T>G	p.Trp38Gly	missense_variant	1/14		NM_001290474.2	ENSP00000497391.1
C2CD2L	ENST00000336702.7	c.112T>G	p.Trp38Gly	missense_variant	1/14	1		ENSP00000338885.3
DPAGT1	ENST00000409993.6	c.-1074A>C		5_prime_UTR_variant	1/11	2		ENSP00000386597.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.112T>G (p.W38G) alteration is located in exon 1 (coding exon 1) of the C2CD2L gene. This alteration results from a T to G substitution at nucleotide position 112, causing the tryptophan (W) at amino acid position 38 to be replaced by a glycine (G). 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	0.15
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	25
DANN	Benign	0.93
DEOGEN2	Benign	0.018	.;T
Eigen	Benign	0.15
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.63	T;T
M_CAP	Pathogenic	0.55	D
MetaRNN	Benign	0.37	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L;L
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-2.0	N;.
REVEL	Benign	0.15
Sift	Uncertain	0.0050	D;.
Sift4G	Uncertain	0.0080	D;.
Polyphen		0.98	D;D
Vest4		0.51
MutPred		0.58		Gain of loop (P = 3e-04);Gain of loop (P = 3e-04);
MVP		0.043
MPC		1.6
ClinPred		0.84	D
GERP RS		4.7
Varity_R		0.42
gMVP		0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-118978563;