9-99221670-CAGCCAGTCCCC-CCGGGGACT

Position:

• chr9-99221670-CAGCCAGTCCCC-CCGGGGACT

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4_Supporting PP5

The NM_033087.4(ALG2):​c.214_224delinsAGTCCCCG​(p.Gly72_Leu75delinsSerProArg) variant causes a protein altering change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. G72G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ALG2 NM_033087.4 protein_altering
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 6.78

Genes affected

ALG2 (HGNC:23159): (ALG2 alpha-1,3/1,6-mannosyltransferase) This gene encodes a member of the glycosyltransferase 1 family. The encoded protein acts as an alpha 1,3 mannosyltransferase, mannosylating Man(2)GlcNAc(2)-dolichol diphosphate and Man(1)GlcNAc(2)-dolichol diphosphate to form Man(3)GlcNAc(2)-dolichol diphosphate. Defects in this gene have been associated with congenital disorder of glycosylation type Ih (CDG-Ii). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_033087.4. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 9-99221671-AGCCAGTCCCC-CGGGGACT is Pathogenic according to our data. Variant chr9-99221671-AGCCAGTCCCC-CGGGGACT is described in ClinVar as [Pathogenic]. Clinvar id is 183018.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ALG2	NM_033087.4	c.214_224delinsAGTCCCCG	p.Gly72_Leu75delinsSerProArg	protein_altering_variant	1/2	ENST00000476832.2
ALG2	NR_024532.2	n.262_272delinsAGTCCCCG		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ALG2	ENST00000476832.2	c.214_224delinsAGTCCCCG	p.Gly72_Leu75delinsSerProArg	protein_altering_variant	1/2	1	NM_033087.4	P1
ALG2	ENST00000238477.5	c.214_224delinsAGTCCCCG	p.Gly72_Leu75delinsSerProArg	protein_altering_variant, NMD_transcript_variant	1/3	2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Congenital myasthenic syndrome 14 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 01, 2014

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs730882123; hg19: chr9-101983953;