rs17602686

Variant names:

• chr15-51377428-A-C
• rs17602686
• NM_181789.4:c.364-21A>C

Your query was ambiguous. Multiple possible variants found:

• chr15-51377428-A-C
• chr15-51377428-A-G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_181789.4(GLDN):​c.364-21A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,607,702 control chromosomes in the GnomAD database, including 30,289 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.15 (1994 hom., cov: 32)
  • Exomes 𝑓: 0.19 (28295 hom.)
• Consequence: GLDN NM_181789.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.67
• Publications: 9 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 -16 ACMG points.

• BP6: Variant 15-51377428-A-C is Benign according to our data. Variant chr15-51377428-A-C is described in ClinVar as Benign. ClinVar VariationId is 1225115.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLDN	NM_181789.4	c.364-21A>C		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.364-21A>C		intron_variant	Intron 1 of 9	2	NM_181789.4	ENSP00000335196.6

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22284 AN: 152090 Hom.: 1995 Cov.: 32

Gnomad AFR AF: 0.0415

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.0822

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.174

GnomAD2 exomes AF: 0.168 AC: 42143 AN: 250168 AF XY: 0.175

Gnomad AFR exome AF: 0.0364

Gnomad AMR exome AF: 0.144

Gnomad ASJ exome AF: 0.188

Gnomad EAS exome AF: 0.0754

Gnomad FIN exome AF: 0.155

Gnomad NFE exome AF: 0.205

Gnomad OTH exome AF: 0.185

GnomAD4 exome AF: 0.192 AC: 279871 AN: 1455494 Hom.: 28295 Cov.: 29 AF XY: 0.193 AC XY: 140063 AN XY: 724412

African (AFR) AF: 0.0327 AC: 1092 AN: 33404

American (AMR) AF: 0.148 AC: 6586 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 4749 AN: 26102

East Asian (EAS) AF: 0.0788 AC: 3125 AN: 39680

South Asian (SAS) AF: 0.186 AC: 16023 AN: 86054

European-Finnish (FIN) AF: 0.152 AC: 8126 AN: 53290

Middle Eastern (MID) AF: 0.220 AC: 1266 AN: 5750

European-Non Finnish (NFE) AF: 0.206 AC: 228023 AN: 1106390

Other (OTH) AF: 0.181 AC: 10881 AN: 60184

GnomAD4 genome AF: 0.146 AC: 22278 AN: 152208 Hom.: 1994 Cov.: 32 AF XY: 0.145 AC XY: 10785 AN XY: 74414

African (AFR) AF: 0.0414 AC: 1722 AN: 41550

American (AMR) AF: 0.169 AC: 2584 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 656 AN: 3470

East Asian (EAS) AF: 0.0822 AC: 426 AN: 5180

South Asian (SAS) AF: 0.177 AC: 855 AN: 4822

European-Finnish (FIN) AF: 0.157 AC: 1660 AN: 10598

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13815 AN: 67978

Other (OTH) AF: 0.174 AC: 367 AN: 2114

Alfa AF: 0.173 Hom.: 3396

Bravo AF: 0.140

TwinsUK AF: 0.204 AC: 756

ALSPAC AF: 0.210 AC: 811

ESP6500AA AF: 0.0453 AC: 199

ESP6500EA AF: 0.210 AC: 1805

ExAC AF: 0.169 AC: 20488

Asia WGS AF: 0.141 AC: 490 AN: 3478

EpiCase AF: 0.216

EpiControl AF: 0.225

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	2.5
DANN	Benign	0.79
FATHMM_MKL	Benign	0.52	D
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.0027	T
PhyloP100		2.7
PROVEAN	Benign	-0.57	N
Sift	Benign	0.50	T
Sift4G	Benign	0.28	T
GERP RS		4.9
La Branchor		0.87
BranchPoint Hunter		4.0
PromoterAI		-0.020	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.36		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.36		Position offset: 21

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

Other links and lift over

dbSNP: rs17602686; hg19: chr15-51669625; COSMIC: COSV59090383; COSMIC: COSV59090383;