chr4-6578556-A-T

Variant names:

• chr4-6578556-A-T
• rs3764809
• NM_015274.3:c.391+58A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015274.3(MAN2B2):​c.391+58A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAN2B2 NM_015274.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• MAN2B2 deficiency

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015274.3. 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
	MAN2B2	NM_015274.3	MANE Select	c.391+58A>T		intron	N/A	NP_056089.1	Q9Y2E5-1
	MAN2B2	NM_001292038.2		c.391+58A>T		intron	N/A	NP_001278967.1	E9PCD7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAN2B2	ENST00000285599.8	TSL:1 MANE Select	c.391+58A>T		intron	N/A	ENSP00000285599.3	Q9Y2E5-1
	MAN2B2	ENST00000868575.1		c.391+58A>T		intron	N/A	ENSP00000538634.1
	MAN2B2	ENST00000868574.1		c.529+58A>T		intron	N/A	ENSP00000538633.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1278232 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 639180

African (AFR) AF: 0.00 AC: 0 AN: 29312

American (AMR) AF: 0.00 AC: 0 AN: 38738

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24408

East Asian (EAS) AF: 0.00 AC: 0 AN: 36374

South Asian (SAS) AF: 0.00 AC: 0 AN: 78710

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48696

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5364

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 962530

Other (OTH) AF: 0.00 AC: 0 AN: 54100

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.051
DANN	Benign	0.53
PhyloP100		-2.1

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

Other links and lift over

dbSNP: rs3764809; hg19: chr4-6580283;