15-75358495-G-C

Variant names:

• chr15-75358495-G-C
• rs1128933
• NM_006715.4:c.2370C>G

Variant summary

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

The NM_006715.4(MAN2C1):​c.2370C>G​(p.Asp790Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D790H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MAN2C1 NM_006715.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410
• Publications: 20 publications found

Genes affected

MAN2C1 (HGNC:6827): (mannosidase alpha class 2C member 1) Predicted to enable alpha-mannosidase activity. Predicted to be involved in oligosaccharide catabolic process. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MAN2C1 Gene-Disease associations (from GenCC):

• congenital disorder of deglycosylation 2

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Illumina, Ambry Genetics, ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006715.4. 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
	MAN2C1	NM_006715.4	MANE Select	c.2370C>G	p.Asp790Glu	missense	Exon 20 of 26	NP_006706.2
	MAN2C1	NM_001256494.2		c.2421C>G	p.Asp807Glu	missense	Exon 20 of 26	NP_001243423.1	Q9NTJ4-4
	MAN2C1	NM_001256495.2		c.2370C>G	p.Asp790Glu	missense	Exon 20 of 26	NP_001243424.1	Q9NTJ4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAN2C1	ENST00000267978.10	TSL:1 MANE Select	c.2370C>G	p.Asp790Glu	missense	Exon 20 of 26	ENSP00000267978.4	Q9NTJ4-1
	MAN2C1	ENST00000565683.5	TSL:1	c.2421C>G	p.Asp807Glu	missense	Exon 20 of 26	ENSP00000457788.1	Q9NTJ4-4
	MAN2C1	ENST00000569482.5	TSL:1	c.2370C>G	p.Asp790Glu	missense	Exon 20 of 26	ENSP00000455998.1	Q9NTJ4-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 66

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.69
PhyloP100		-0.041
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.38
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.44		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.44		Position offset: 0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1128933; hg19: chr15-75650836;