Variant 19-12649904-ACC-AC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_000528.4(MAN2B1):c.2267+8delG variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000261 in 1,535,298 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0000075 ( 0 hom., cov: 28)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MAN2B1
NM_000528.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.840

Variant links:

Genes affected

MAN2B1 (HGNC:6826): (mannosidase alpha class 2B member 1) This gene encodes an enzyme that hydrolyzes terminal, non-reducing alpha-D-mannose residues in alpha-D-mannosides. Its activity is necessary for the catabolism of N-linked carbohydrates released during glycoprotein turnover and it is member of family 38 of glycosyl hydrolases. The full length protein is processed in two steps. First, a 49 aa leader sequence is cleaved off and the remainder of the protein is processed into 3 peptides of 70 kDa, 42 kDa (D) and 13/15 kDa (E). Next, the 70 kDa peptide is further processed into three peptides (A, B and C). The A, B and C peptides are disulfide-linked. Defects in this gene have been associated with lysosomal alpha-mannosidosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2010]

MAN2B1 links:

MAN2B1 (HGNC:):

MAN2B1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 19-12649904-AC-A is Benign according to our data. Variant chr19-12649904-AC-A is described in ClinVar as [Benign]. Clinvar id is 2996167.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-12649904-AC-A is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
MAN2B1	NM_000528.4 linkuse as main transcript	c.2267+8delG	splice_region_variant, intron_variant	ENST00000456935.7	NP_000519.2	O00754-1
MAN2B1	NM_001173498.2 linkuse as main transcript	c.2264+8delG	splice_region_variant, intron_variant		NP_001166969.1	O00754-2A8K6A7
MAN2B1	XM_005259913.3 linkuse as main transcript	c.2270+8delG	splice_region_variant, intron_variant		XP_005259970.1
MAN2B1	XM_047438841.1 linkuse as main transcript	c.1166+8delG	splice_region_variant, intron_variant		XP_047294797.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MAN2B1	ENST00000456935.7 linkuse as main transcript	c.2267+8delG	splice_region_variant, intron_variant	1	NM_000528.4	ENSP00000395473.2	O00754-1
MAN2B1	ENST00000221363.8 linkuse as main transcript	c.2264+8delG	splice_region_variant, intron_variant	1		ENSP00000221363.4	O00754-2
MAN2B1	ENST00000466794.5 linkuse as main transcript	n.2857+8delG	splice_region_variant, intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00000747

AC:

AN:

133872

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000120

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000214

AC:

AN:

1401426

Hom.:

Cov.:

AF XY:

0.00000286

AC XY:

AN XY:

698456

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000188

Gnomad4 OTH exome

AF:

0.0000175

GnomAD4 genome

AF:

0.00000747

AC:

AN:

133872

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

64792

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000120

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Deficiency of alpha-mannosidase

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 04, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over