11-119107898-G-T

Variant names:

• chr11-119107898-G-T
• NM_001290474.2:c.157G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001290474.2(C2CD2L):​c.157G>T​(p.Ala53Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000728 in 1,373,024 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: C2CD2L NM_001290474.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.60
• Publications: 0 publications found

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]

DPAGT1 Gene-Disease associations (from GenCC):

• congenital myasthenic syndrome 13

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P
• DPAGT1-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, ClinGen
• congenital myasthenic syndromes with glycosylation defect

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15271273).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290474.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2CD2L	NM_001290474.2	MANE Select	c.157G>T	p.Ala53Ser	missense	Exon 1 of 14	NP_001277403.1	O14523-1
	C2CD2L	NM_014807.5		c.157G>T	p.Ala53Ser	missense	Exon 1 of 14	NP_055622.3
	C2CD2L	NM_001382613.1		c.157G>T	p.Ala53Ser	missense	Exon 2 of 15	NP_001369542.1	O14523-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2CD2L	ENST00000648610.2	MANE Select	c.157G>T	p.Ala53Ser	missense	Exon 1 of 14	ENSP00000497391.1	O14523-1
	C2CD2L	ENST00000336702.7	TSL:1	c.157G>T	p.Ala53Ser	missense	Exon 1 of 14	ENSP00000338885.3	O14523-2
	C2CD2L	ENST00000861321.1		c.157G>T	p.Ala53Ser	missense	Exon 1 of 14	ENSP00000531380.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.28e-7 AC: 1 AN: 1373024 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 679632

African (AFR) AF: 0.00 AC: 0 AN: 27696

American (AMR) AF: 0.00 AC: 0 AN: 31246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23956

East Asian (EAS) AF: 0.00 AC: 0 AN: 31674

South Asian (SAS) AF: 0.00 AC: 0 AN: 77966

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4182

European-Non Finnish (NFE) AF: 9.30e-7 AC: 1 AN: 1075364

Other (OTH) AF: 0.00 AC: 0 AN: 56706

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Benign	0.82
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.49	T
M_CAP	Uncertain	0.22	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		3.6
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.026
Sift	Benign	0.27	T
Sift4G	Benign	0.57	T
Polyphen		0.36	B
Vest4		0.087
MutPred		0.21		Gain of glycosylation at A53 (P = 0.0072)
MVP		0.082
MPC		0.45
ClinPred		0.42	T
GERP RS		3.9
PromoterAI		0.13	Neutral
Varity_R		0.071
gMVP		0.26
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr11-118978608;