11-119107920-T-C

Variant names:

• chr11-119107920-T-C
• rs780563976
• NM_001290474.2:c.179T>C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001290474.2(C2CD2L):​c.179T>C​(p.Leu60Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000587 in 1,534,362 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: 𝑓 0.000092 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000055 (0 hom.)
• Consequence: C2CD2L NM_001290474.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.163

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04318437).
• BS2: High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C2CD2L	NM_001290474.2	c.179T>C	p.Leu60Pro	missense_variant	Exon 1 of 14	ENST00000648610.2	NP_001277403.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2CD2L	ENST00000648610.2	c.179T>C	p.Leu60Pro	missense_variant	Exon 1 of 14		NM_001290474.2	ENSP00000497391.1

Frequencies

GnomAD3 genomes AF: 0.0000924 AC: 14 AN: 151520 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000170

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: 0.0000886

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000455 AC: 6 AN: 131994 Hom.: 0 AF XY: 0.0000132 AC XY: 1 AN XY: 75722

Gnomad AFR exome AF: 0.000281

Gnomad AMR exome AF: 0.000102

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: 0.0000371

Gnomad OTH exome AF: 0.000307

GnomAD4 exome AF: 0.0000550 AC: 76 AN: 1382842 Hom.: 0 Cov.: 32 AF XY: 0.0000540 AC XY: 37 AN XY: 685276

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000159

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000621

Gnomad4 OTH exome AF: 0.0000702

GnomAD4 genome AF: 0.0000924 AC: 14 AN: 151520 Hom.: 0 Cov.: 31 AF XY: 0.0000946 AC XY: 7 AN XY: 74020

Gnomad4 AFR AF: 0.000170

Gnomad4 AMR AF: 0.0000655

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000886

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000573 Hom.: 0

Bravo AF: 0.000110

ExAC AF: 0.0000181 AC: 2

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 20, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.179T>C (p.L60P) alteration is located in exon 1 (coding exon 1) of the C2CD2L gene. This alteration results from a T to C substitution at nucleotide position 179, causing the leucine (L) at amino acid position 60 to be replaced by a proline (P). 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	0.075
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Benign	0.68
DEOGEN2	Benign	0.0058	.;T
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.54	T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.043	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.060	N;.
REVEL	Benign	0.030
Sift	Benign	0.18	T;.
Sift4G	Uncertain	0.041	D;.
Polyphen		0.0	B;B
Vest4		0.12
MutPred		0.33		Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);
MVP		0.043
MPC		0.78
ClinPred		0.016	T
GERP RS		2.2
Varity_R		0.36
gMVP		0.72

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

Other links and lift over

dbSNP: rs780563976; hg19: chr11-118978630;