Variant 4-6576760-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_015274.3(MAN2B2):c.285+36A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.833 in 1,607,672 control chromosomes in the GnomAD database, including 559,059 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.82 ( 50862 hom., cov: 33)

Exomes 𝑓: 0.84 ( 508197 hom. )

Consequence

MAN2B2
NM_015274.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.28

Variant links:

Genes affected

MAN2B2 (HGNC:29623): (mannosidase alpha class 2B member 2) Predicted to enable alpha-mannosidase activity. Predicted to be involved in mannose metabolic process. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

MAN2B2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BP6

Variant 4-6576760-A-G is Benign according to our data. Variant chr4-6576760-A-G is described in ClinVar as [Benign]. Clinvar id is 2688204.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAN2B2	NM_015274.3 linkuse as main transcript	c.285+36A>G		intron_variant		ENST00000285599.8
MAN2B2	NM_001292038.2 linkuse as main transcript	c.285+36A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
MAN2B2	ENST00000285599.8 linkuse as main transcript	c.285+36A>G	intron_variant	1	NM_015274.3	P1	Q9Y2E5-1
MAN2B2	ENST00000504248.5 linkuse as main transcript	c.285+36A>G	intron_variant	2
MAN2B2	ENST00000505907.1 linkuse as main transcript	c.281+36A>G	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.816

AC:

124056

AN:

152016

Hom.:

50815

Cov.:

show subpopulations

Gnomad AFR

AF:

0.749

Gnomad AMI

AF:

0.884

Gnomad AMR

AF:

0.819

Gnomad ASJ

AF:

0.873

Gnomad EAS

AF:

0.856

Gnomad SAS

AF:

0.838

Gnomad FIN

AF:

0.873

Gnomad MID

AF:

0.810

Gnomad NFE

AF:

0.840

Gnomad OTH

AF:

0.796

GnomAD3 exomes

AF:

0.839

AC:

209401

AN:

249528

Hom.:

88083

AF XY:

0.840

AC XY:

113490

AN XY:

135112

show subpopulations

Gnomad AFR exome

AF:

0.748

Gnomad AMR exome

AF:

0.868

Gnomad ASJ exome

AF:

0.870

Gnomad EAS exome

AF:

0.859

Gnomad SAS exome

AF:

0.833

Gnomad FIN exome

AF:

0.867

Gnomad NFE exome

AF:

0.834

Gnomad OTH exome

AF:

0.833

GnomAD4 exome

AF:

0.835

AC:

1215564

AN:

1455538

Hom.:

508197

Cov.:

AF XY:

0.835

AC XY:

603732

AN XY:

722914

show subpopulations

Gnomad4 AFR exome

AF:

0.754

Gnomad4 AMR exome

AF:

0.864

Gnomad4 ASJ exome

AF:

0.875

Gnomad4 EAS exome

AF:

0.851

Gnomad4 SAS exome

AF:

0.835

Gnomad4 FIN exome

AF:

0.868

Gnomad4 NFE exome

AF:

0.833

Gnomad4 OTH exome

AF:

0.836

GnomAD4 genome

AF:

0.816

AC:

124163

AN:

152134

Hom.:

50862

Cov.:

AF XY:

0.816

AC XY:

60652

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.749

Gnomad4 AMR

AF:

0.820

Gnomad4 ASJ

AF:

0.873

Gnomad4 EAS

AF:

0.857

Gnomad4 SAS

AF:

0.839

Gnomad4 FIN

AF:

0.873

Gnomad4 NFE

AF:

0.840

Gnomad4 OTH

AF:

0.799

Alfa

AF:

0.836

Hom.:

27589

Bravo

AF:

0.811

Asia WGS

AF:

0.850

AC:

2956

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 99% of patients studied by a panel of primary immunodeficiencies. Number of patients: 94. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

1.2

DANN

Benign

0.41

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

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