rs780828430

Variant names:

• chr8-74351471-TG-T
• rs780828430
• NM_018972.4:c.310+6delG

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_018972.4(GDAP1):​c.310+6delG variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00108 in 1,602,702 control chromosomes in the GnomAD database, including 1 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (1 hom.)
• Consequence: GDAP1 NM_018972.4 splice_region, intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4 B:6
• Conservation: PhyloP100: 6.18
• Publications: 0 publications found

Genes affected

GDAP1 (HGNC:15968): (ganglioside induced differentiation associated protein 1) This gene encodes a member of the ganglioside-induced differentiation-associated protein family, which may play a role in a signal transduction pathway during neuronal development. Mutations in this gene have been associated with various forms of Charcot-Marie-Tooth Disease and neuropathy. Two transcript variants encoding different isoforms and a noncoding variant have been identified for this gene. [provided by RefSeq, Feb 2012]

GDAP1 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease

  Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
• Charcot-Marie-Tooth disease axonal type 2K

  Inheritance: AD, AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• Charcot-Marie-Tooth disease recessive intermediate A

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• autosomal dominant Charcot-Marie-Tooth disease type 2K

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Charcot-Marie-Tooth disease type 4A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP6: Variant 8-74351471-TG-T is Benign according to our data. Variant chr8-74351471-TG-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 245606.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018972.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDAP1	NM_018972.4	MANE Select	c.310+6delG		splice_region intron	N/A	NP_061845.2
	GDAP1	NM_001362930.2		c.310+6delG		splice_region intron	N/A	NP_001349859.1
	GDAP1	NM_001040875.4		c.106+6delG		splice_region intron	N/A	NP_001035808.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDAP1	ENST00000220822.12	TSL:1 MANE Select	c.310+6delG		splice_region intron	N/A	ENSP00000220822.7
	GDAP1	ENST00000434412.3	TSL:1	c.178+6delG		splice_region intron	N/A	ENSP00000417006.3
	GDAP1	ENST00000524366.6	TSL:3	n.352delG		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.00102 AC: 155 AN: 152238 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00662

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00169

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000970 AC: 244 AN: 251448 AF XY: 0.000912

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000173

Gnomad ASJ exome AF: 0.00585

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000601

Gnomad NFE exome AF: 0.00141

Gnomad OTH exome AF: 0.000651

GnomAD4 exome AF: 0.00109 AC: 1575 AN: 1450346 Hom.: 1 Cov.: 29 AF XY: 0.00109 AC XY: 790 AN XY: 722374

African (AFR) AF: 0.0000903 AC: 3 AN: 33212

American (AMR) AF: 0.000224 AC: 10 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00507 AC: 132 AN: 26052

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.00 AC: 0 AN: 86016

European-Finnish (FIN) AF: 0.000412 AC: 22 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00121 AC: 1329 AN: 1101508

Other (OTH) AF: 0.00132 AC: 79 AN: 60034

GnomAD4 genome AF: 0.00102 AC: 155 AN: 152356 Hom.: 0 Cov.: 33 AF XY: 0.000792 AC XY: 59 AN XY: 74510

African (AFR) AF: 0.0000962 AC: 4 AN: 41592

American (AMR) AF: 0.000196 AC: 3 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00662 AC: 23 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00169 AC: 115 AN: 68032

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.00193 Hom.: 0

Bravo AF: 0.000790

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00147

EpiControl AF: 0.00119

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:4 Benign:6

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Charcot-Marie-Tooth disease axonal type 2K Uncertain:1 Benign:1

Aug 12, 2021

Laboratory of Functional Genomics, Research Centre for Medical Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing;in vitro

Splicing variant c.310+6delG in GDAP1 gene could be classified as likely benign variant according to AСMG criteria (PM2, BP4, BS3, PM3). The variant vas observed in 31 y.o. female patient with Charcot-Marie-Tooth disease with axonal type of lession in compound heterozygous state with pathogenic c.715C>T variant.

Nov 03, 2018

Baylor Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].

not provided Benign:2

Jun 16, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Sep 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

GDAP1: BP4

Inborn genetic diseases Uncertain:1

Dec 07, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.310+6delG intronic variant is located 6 nucleotides after coding exon 2 of the GDAP1 gene. This variant results from a deletion of one nucleotide at position c.310+6. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Based on the supporting evidence, this variant is unlikely to be causative of axonal Charcot-Marie-Tooth disease, type 2K (CMT2K); however, its contribution to the development of the autosomal recessive spectrum of diseases is uncertain.

Charcot-Marie-Tooth with Vocal Cord Paresis Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Charcot-Marie-Tooth, Intermediate Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Charcot-Marie-Tooth disease Benign:1

Molecular Genetics Laboratory, London Health Sciences Centre

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Charcot-Marie-Tooth disease type 4A Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

GDAP1-related disorder Benign:1

Jul 01, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.2
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs780828430; hg19: chr8-75263706;