rs2124873

Variant names:

• chr15-51356337-G-A
• rs2124873
• NM_181789.4:c.363+14290G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-51356337-G-A
• chr15-51356337-G-C
• chr15-51356337-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181789.4(GLDN):​c.363+14290G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,076 control chromosomes in the GnomAD database, including 2,903 homozygotes. 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: 𝑓 0.18 (2903 hom., cov: 31)
• Consequence: GLDN NM_181789.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 3 publications found

Genes affected

GLDN (HGNC:29514): (gliomedin) This gene encodes a protein that contains olfactomedin-like and collagen-like domains. The encoded protein, which exists in both transmembrane and secreted forms, promotes formation of the nodes of Ranvier in the peripheral nervous system. Mutations in this gene cause a form of lethal congenital contracture syndrome in human patients. Autoantibodies to the encoded protein have been identified in sera form patients with multifocal motor neuropathy. [provided by RefSeq, May 2017]

GLDN Gene-Disease associations (from GenCC):

• lethal congenital contracture syndrome 11

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLDN	NM_181789.4	c.363+14290G>A		intron_variant	Intron 1 of 9	ENST00000335449.11	NP_861454.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLDN	ENST00000335449.11	c.363+14290G>A		intron_variant	Intron 1 of 9	2	NM_181789.4	ENSP00000335196.6
GLDN	ENST00000558286.5	n.174+14290G>A		intron_variant	Intron 1 of 2	1
GLDN	ENST00000560690.5	n.140+14252G>A		intron_variant	Intron 1 of 3	1
GLDN	ENST00000560215.5	c.249+14290G>A		intron_variant	Intron 1 of 3	4		ENSP00000484633.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27011 AN: 151958 Hom.: 2897 Cov.: 31

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.191

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.178 AC: 27047 AN: 152076 Hom.: 2903 Cov.: 31 AF XY: 0.182 AC XY: 13490 AN XY: 74304

African (AFR) AF: 0.118 AC: 4897 AN: 41490

American (AMR) AF: 0.238 AC: 3631 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 591 AN: 3470

East Asian (EAS) AF: 0.491 AC: 2528 AN: 5152

South Asian (SAS) AF: 0.353 AC: 1693 AN: 4802

European-Finnish (FIN) AF: 0.112 AC: 1180 AN: 10578

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11917 AN: 67998

Other (OTH) AF: 0.195 AC: 412 AN: 2112

Alfa AF: 0.182 Hom.: 4492

Bravo AF: 0.185

Asia WGS AF: 0.417 AC: 1447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.37
DANN	Benign	0.61
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2124873; hg19: chr15-51648534;