rs34637446

Variant names:

• chr7-2513247-AGATGGATGGATGGATG-A
• NM_001166355.2:c.151_166delGATGGATGGATGGATG

Your query was ambiguous. Multiple possible variants found:

• chr7-2513247-AGATGGATGGATGGATG-A
• chr7-2513247-AGATGGATGGATGGATG-AGATG
• chr7-2513247-AGATGGATGGATGGATG-AGATGGATG
• chr7-2513247-AGATGGATGGATGGATG-AGATGGATGGATG
• chr7-2513247-AGATGGATGGATGGATG-AGATGGATGGATGGATGGATG
• chr7-2513247-AGATGGATGGATGGATG-AGATGGATGGATGGATGGATGGATG
• chr7-2513247-AGATGGATGGATGGATG-AGATGGATGGATGGATGGATGGATGGATG

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001166355.2(LFNG):​c.151_166delGATGGATGGATGGATG​(p.Asp51SerfsTer141) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,433,094 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: LFNG NM_001166355.2 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46

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]

ACMG classification

Verdict is Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LFNG	NM_001166355.2	c.151_166delGATGGATGGATGGATG	p.Asp51SerfsTer141	frameshift_variant	Exon 2 of 9		NP_001159827.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LFNG	ENST00000402506.5	c.151_166delGATGGATGGATGGATG	p.Asp51SerfsTer141	frameshift_variant	Exon 2 of 9	2		ENSP00000385764.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1433094 Hom.: 0 AF XY: 0.00000140 AC XY: 1 AN XY: 713272

Gnomad4 AFR exome AF: 0.0000311

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-2552881;