11-119108092-C-T

Variant names:

• chr11-119108092-C-T
• rs550794219
• NM_001290474.2:c.351C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001290474.2(C2CD2L):​c.351C>T​(p.Asn117Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,437,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: C2CD2L NM_001290474.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP7: Synonymous conserved (PhyloP=1.08 with no splicing effect.

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.351C>T	p.Asn117Asn	synonymous	Exon 1 of 14	NP_001277403.1	O14523-1
	C2CD2L	NM_014807.5		c.351C>T	p.Asn117Asn	synonymous	Exon 1 of 14	NP_055622.3
	C2CD2L	NM_001382613.1		c.351C>T	p.Asn117Asn	synonymous	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.351C>T	p.Asn117Asn	synonymous	Exon 1 of 14	ENSP00000497391.1	O14523-1
	C2CD2L	ENST00000336702.7	TSL:1	c.351C>T	p.Asn117Asn	synonymous	Exon 1 of 14	ENSP00000338885.3	O14523-2
	C2CD2L	ENST00000861321.1		c.351C>T	p.Asn117Asn	synonymous	Exon 1 of 14	ENSP00000531380.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1437562 Hom.: 0 Cov.: 29 AF XY: 0.00000140 AC XY: 1 AN XY: 715822

African (AFR) AF: 0.00 AC: 0 AN: 30520

American (AMR) AF: 0.00 AC: 0 AN: 42466

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25268

East Asian (EAS) AF: 0.00 AC: 0 AN: 36246

South Asian (SAS) AF: 0.00 AC: 0 AN: 85170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51786

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 9.08e-7 AC: 1 AN: 1101048

Other (OTH) AF: 0.00 AC: 0 AN: 59362

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	12
DANN	Benign	0.90
PhyloP100		1.1
PromoterAI		0.011	Neutral

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

Other links and lift over

dbSNP: rs550794219; hg19: chr11-118978802;