Variant chr8-74361906-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_018972.4(GDAP1):c.507T>G(p.Ser169Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,593,766 control chromosomes in the GnomAD database, including 78,134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5924 hom., cov: 33)

Exomes 𝑓: 0.31 ( 72210 hom. )

Consequence

GDAP1
NM_018972.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts U:2B:10

Conservation

PhyloP100: -0.915

Variant links:

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 links:

GDAP1 (HGNC:):

GDAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 8-74361906-T-G is Benign according to our data. Variant chr8-74361906-T-G is described in ClinVar as [Benign]. Clinvar id is 261065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-74361906-T-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.915 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDAP1	NM_018972.4 linkuse as main transcript	c.507T>G	p.Ser169Ser	synonymous_variant	4/6	ENST00000220822.12	NP_061845.2	Q8TB36-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDAP1	ENST00000220822.12 linkuse as main transcript	c.507T>G	p.Ser169Ser	synonymous_variant	4/6	1	NM_018972.4	ENSP00000220822.7		Q8TB36-1

Frequencies

GnomAD3 genomes

AF:

0.260

AC:

39562

AN:

152060

Hom.:

5924

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.314

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.307

Gnomad EAS

AF:

0.312

Gnomad SAS

AF:

0.210

Gnomad FIN

AF:

0.333

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.336

Gnomad OTH

AF:

0.279

GnomAD3 exomes

AF:

0.279

AC:

70092

AN:

251004

Hom.:

10687

AF XY:

0.283

AC XY:

38405

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.185

Gnomad ASJ exome

AF:

0.283

Gnomad EAS exome

AF:

0.323

Gnomad SAS exome

AF:

0.209

Gnomad FIN exome

AF:

0.328

Gnomad NFE exome

AF:

0.332

Gnomad OTH exome

AF:

0.306

GnomAD4 exome

AF:

0.309

AC:

446116

AN:

1441588

Hom.:

72210

Cov.:

AF XY:

0.307

AC XY:

220652

AN XY:

718540

show subpopulations

Gnomad4 AFR exome

AF:

0.107

Gnomad4 AMR exome

AF:

0.194

Gnomad4 ASJ exome

AF:

0.287

Gnomad4 EAS exome

AF:

0.278

Gnomad4 SAS exome

AF:

0.208

Gnomad4 FIN exome

AF:

0.332

Gnomad4 NFE exome

AF:

0.330

Gnomad4 OTH exome

AF:

0.294

GnomAD4 genome

AF:

0.260

AC:

39579

AN:

152178

Hom.:

5924

Cov.:

AF XY:

0.260

AC XY:

19375

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.117

Gnomad4 AMR

AF:

0.241

Gnomad4 ASJ

AF:

0.307

Gnomad4 EAS

AF:

0.313

Gnomad4 SAS

AF:

0.210

Gnomad4 FIN

AF:

0.333

Gnomad4 NFE

AF:

0.336

Gnomad4 OTH

AF:

0.281

Alfa

AF:

0.284

Hom.:

3869

Bravo

AF:

0.246

Asia WGS

AF:

0.256

AC:

892

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Uncertain:2Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 22, 2021	- -
Uncertain significance, no assertion criteria provided	literature only	Inherited Neuropathy Consortium	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Charcot-Marie-Tooth disease axonal type 2K

Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Inherited Neuropathy Consortium Ii, University Of Miami

Jan 06, 2016

- -

Charcot-Marie-Tooth disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

- -

Charcot-Marie-Tooth disease recessive intermediate A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Charcot-Marie-Tooth disease type 4A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, autosomal recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

5.4

DANN

Benign

0.76

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over