4-6575293-G-C

Variant names:

• chr4-6575293-G-C
• rs762352744
• NM_015274.3:c.83G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015274.3(MAN2B2):​c.83G>C​(p.Arg28Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,418,414 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MAN2B2 NM_015274.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.909

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35127228).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAN2B2	NM_015274.3	c.83G>C	p.Arg28Pro	missense_variant	Exon 1 of 19	ENST00000285599.8	NP_056089.1
MAN2B2	NM_001292038.2	c.83G>C	p.Arg28Pro	missense_variant	Exon 1 of 19		NP_001278967.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAN2B2	ENST00000285599.8	c.83G>C	p.Arg28Pro	missense_variant	Exon 1 of 19	1	NM_015274.3	ENSP00000285599.3
MAN2B2	ENST00000504248.5	c.83G>C	p.Arg28Pro	missense_variant	Exon 1 of 19	2		ENSP00000423129.1
MAN2B2	ENST00000505907.1	c.77G>C	p.Arg26Pro	missense_variant	Exon 1 of 17	2		ENSP00000426273.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000212 AC: 3 AN: 1418414 Hom.: 0 Cov.: 31 AF XY: 0.00000285 AC XY: 2 AN XY: 702874

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: 0.00000274

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000844 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Benign	0.90
DEOGEN2	Benign	0.19	T;.
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.23
Sift	Benign	0.10	T;D
Sift4G	Uncertain	0.041	D;D
Polyphen		0.92	P;P
Vest4		0.50
MutPred		0.61		Gain of disorder (P = 0.1553);Gain of disorder (P = 0.1553);
MVP		0.21
MPC		0.57
ClinPred		0.89	D
GERP RS		0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.93
gMVP		0.83

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

Other links and lift over

dbSNP: rs762352744; hg19: chr4-6577020;