rs730882123

chr9-99221670-CAGCCAGTCCCC-CCGGGGACT

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP5

The NM_033087.4(ALG2):c.214_224delinsAGTCCCCG(p.Gly72_Leu75delinsSerProArg) variant causes a protein altering change. 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 1 ACMG points.

• 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

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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;