NM_001166355.2:c.163_166dupGATG

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001166355.2(LFNG):c.163_166dupGATG(p.Glu56GlyfsTer2) variant causes a frameshift, stop gained 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, stop_gained

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:1B:6

Conservation

PhyloP100: 0.00

Publications

13 publications found

Variant links:

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]

LFNG Gene-Disease associations (from GenCC):

spondylocostal dysostosis 3, autosomal recessive
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
autosomal recessive spondylocostal dysostosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LFNG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 7-2513247-A-AGATG is Benign according to our data. Variant chr7-2513247-A-AGATG is described in ClinVar as Benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
LFNG	NM_001166355.2 link	c.163_166dupGATG	p.Glu56GlyfsTer2	frameshift_variant, stop_gained	Exon 2 of 9		NP_001159827.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LFNG	ENST00000402506.5 link	c.163_166dupGATG	p.Glu56GlyfsTer2	frameshift_variant, stop_gained	Exon 2 of 9	2		ENSP00000385764.1

Frequencies

GnomAD3 genomes

AF:

0.342

AC:

51622

AN:

150984

Hom.:

9195

Cov.:

show subpopulations

Gnomad AFR

AF:

0.449

Gnomad AMI

AF:

0.175

Gnomad AMR

AF:

0.248

Gnomad ASJ

AF:

0.327

Gnomad EAS

AF:

0.487

Gnomad SAS

AF:

0.269

Gnomad FIN

AF:

0.315

Gnomad MID

AF:

0.309

Gnomad NFE

AF:

0.301

Gnomad OTH

AF:

0.324

GnomAD4 exome

AF:

0.293

AC:

419070

AN:

1432236

Hom.:

54768

Cov.:

AF XY:

0.291

AC XY:

207635

AN XY:

712858

show subpopulations

African (AFR)

AF:

0.427

AC:

13686

AN:

32082

American (AMR)

AF:

0.198

AC:

8786

AN:

44376

Ashkenazi Jewish (ASJ)

AF:

0.320

AC:

8198

AN:

25626

East Asian (EAS)

AF:

0.509

AC:

19572

AN:

38418

South Asian (SAS)

AF:

0.242

AC:

20550

AN:

84934

European-Finnish (FIN)

AF:

0.299

AC:

15687

AN:

52488

Middle Eastern (MID)

AF:

0.318

AC:

1801

AN:

5662

European-Non Finnish (NFE)

AF:

0.287

AC:

312948

AN:

1089532

Other (OTH)

AF:

0.302

AC:

17842

AN:

59118

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

15057

30114

45170

60227

75284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10748

21496

32244

42992

53740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.342

AC:

51637

AN:

151100

Hom.:

9199

Cov.:

AF XY:

0.340

AC XY:

25045

AN XY:

73762

show subpopulations

African (AFR)

AF:

0.448

AC:

18391

AN:

41032

American (AMR)

AF:

0.248

AC:

3772

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.327

AC:

1130

AN:

3460

East Asian (EAS)

AF:

0.486

AC:

2473

AN:

5086

South Asian (SAS)

AF:

0.268

AC:

1281

AN:

4778

European-Finnish (FIN)

AF:

0.315

AC:

3288

AN:

10450

Middle Eastern (MID)

AF:

0.308

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.301

AC:

20381

AN:

67772

Other (OTH)

AF:

0.321

AC:

672

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1649

3298

4946

6595

8244

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

500

1000

1500

2000

2500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.222

Hom.:

525

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:3

Nov 25, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 16, 2018

Gharavi Laboratory, Columbia University

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:research

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:3

Jun 25, 2020

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0

Mutation Taster

=172/28

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over