7-2513247-AGATGGATGGATG-AGATGGATGGATGGATG
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 8P and 16B. PVS1BP6_Very_StrongBA1
The NM_001166355.2(LFNG):c.163_166dup(p.Glu56GlyfsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,583,336 control chromosomes in the GnomAD database, including 63,967 homozygotes. Variant has been reported in ClinVar as Benign (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.34 ( 9199 hom., cov: 0)
Exomes 𝑓: 0.29 ( 54768 hom. )
Consequence
LFNG
NM_001166355.2 frameshift
NM_001166355.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.00
Genes affected
LFNG (HGNC:6560): (LFNG O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase) This gene is a member of the glycosyltransferase 31 gene family. Members of this gene family, which also includes the MFNG (GeneID: 4242) and RFNG (GeneID: 5986) genes, encode evolutionarily conserved glycosyltransferases that act in the Notch signaling pathway to define boundaries during embryonic development. While their genomic structure is distinct from other glycosyltransferases, these proteins have a fucose-specific beta-1,3-N-acetylglucosaminyltransferase activity that leads to elongation of O-linked fucose residues on Notch, which alters Notch signaling. The protein encoded by this gene is predicted to be a single-pass type II Golgi membrane protein but it may also be secreted and proteolytically processed like the related proteins in mouse and Drosophila (PMID: 9187150). Mutations in this gene have been associated with autosomal recessive spondylocostal dysostosis 3. [provided by RefSeq, May 2018]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
BP6
Variant 7-2513247-A-AGATG is Benign according to our data. Variant chr7-2513247-A-AGATG is described in ClinVar as [Benign]. Clinvar id is 591286.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LFNG | NM_001166355.2 | c.163_166dup | p.Glu56GlyfsTer2 | frameshift_variant | 2/9 | NP_001159827.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LFNG | ENST00000402506.5 | c.163_166dup | p.Glu56GlyfsTer2 | frameshift_variant | 2/9 | 2 | ENSP00000385764 |
Frequencies
GnomAD3 genomes AF: 0.342 AC: 51622AN: 150984Hom.: 9195 Cov.: 0
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GnomAD4 exome AF: 0.293 AC: 419070AN: 1432236Hom.: 54768 Cov.: 34 AF XY: 0.291 AC XY: 207635AN XY: 712858
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GnomAD4 genome AF: 0.342 AC: 51637AN: 151100Hom.: 9199 Cov.: 0 AF XY: 0.340 AC XY: 25045AN XY: 73762
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ClinVar
Significance: Benign
Submissions summary: Uncertain:1Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:3
Uncertain significance, no assertion criteria provided | research | Gharavi Laboratory, Columbia University | Sep 16, 2018 | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 25, 2020 | - - |
not specified Benign:2
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital | Jun 25, 2020 | - - |
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at