chr4-6575322-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM1BS2
The NM_015274.3(MAN2B2):c.112G>A(p.Asp38Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000232 in 1,584,442 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_015274.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MAN2B2 | ENST00000285599.8 | c.112G>A | p.Asp38Asn | missense_variant | Exon 1 of 19 | 1 | NM_015274.3 | ENSP00000285599.3 | ||
MAN2B2 | ENST00000504248.5 | c.112G>A | p.Asp38Asn | missense_variant | Exon 1 of 19 | 2 | ENSP00000423129.1 | |||
MAN2B2 | ENST00000505907.1 | c.106G>A | p.Asp36Asn | missense_variant | Exon 1 of 17 | 2 | ENSP00000426273.1 |
Frequencies
GnomAD3 genomes AF: 0.000171 AC: 26AN: 152246Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000291 AC: 58AN: 199310Hom.: 0 AF XY: 0.000319 AC XY: 35AN XY: 109630
GnomAD4 exome AF: 0.000238 AC: 341AN: 1432078Hom.: 2 Cov.: 31 AF XY: 0.000239 AC XY: 170AN XY: 710966
GnomAD4 genome AF: 0.000171 AC: 26AN: 152364Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12AN XY: 74506
ClinVar
Submissions by phenotype
not provided Uncertain:2
- -
- -
not specified Uncertain:1
Variant summary: MAN2B2 c.112G>A (p.Asp38Asn) results in a conservative amino acid change located in the Glycoside hydrosylase family 38, N-terminal domain (IPR000602) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00029 in 199310 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in MAN2B2 causing MAN2B2 Deficiency, allowing no conclusion about variant significance. c.112G>A has been reported in the literature in individuals affected with MAN2B2 Deficiency. These report(s) do not provide unequivocal conclusions about association of the variant with MAN2B2 Deficiency. Co-occurrences with other pathogenic variant(s) have been reported (DNM1 c.97C>T, p.Gln33*), providing supporting evidence for a benign role. At least one publication reports experimental evidence evaluating an impact on protein function, however, does not allow convincing conclusions about the variant effect. The following publications have been ascertained in the context of this evaluation (PMID: 31775018, 34172529). ClinVar contains an entry for this variant (Variation ID: 1065157). Based on the evidence outlined above, the variant was classified as uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at