Genetic Variant GDAP1:c.-237dupA (chr8-74350205-T-TA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The ENST00000675944.1(GDAP1):c.-237dupA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.49 ( 17707 hom., cov: 0)

Consequence

GDAP1
ENST00000675944.1 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.410

Publications

1 publications found

Variant links:

COSMIC-nc: COSV55186763

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

GDAP1 links:

ENSG00000253596 (HGNC:):

ENSG00000253596 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 8-74350205-T-TA is Benign according to our data. Variant chr8-74350205-T-TA is described in ClinVar as Benign. ClinVar VariationId is 1263644.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000675944.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GDAP1	NM_018972.4	MANE Select	c.-257_-256insA	upstream_gene	N/A	NP_061845.2	Q8TB36-1
GDAP1	NM_001362930.2		c.-257_-256insA	upstream_gene	N/A	NP_001349859.1	A0A6Q8PEZ4
GDAP1	NM_001040875.4		c.-331_-330insA	upstream_gene	N/A	NP_001035808.1	Q8TB36-2

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
GDAP1	ENST00000675944.1	c.-237dupA	5_prime_UTR	Exon 1 of 6	ENSP00000502673.1	Q8TB36-2
GDAP1	ENST00000674806.1	c.-215dupA	5_prime_UTR	Exon 1 of 6	ENSP00000502637.1	B4DIH2
GDAP1	ENST00000674612.1	c.-17-9921dupA	intron	N/A	ENSP00000501864.1	B4DIH2

Frequencies

GnomAD3 genomes

AF:

0.491

AC:

72117

AN:

146758

Hom.:

17699

Cov.:

show subpopulations

Gnomad AFR

AF:

0.446

Gnomad AMI

AF:

0.413

Gnomad AMR

AF:

0.558

Gnomad ASJ

AF:

0.474

Gnomad EAS

AF:

0.592

Gnomad SAS

AF:

0.428

Gnomad FIN

AF:

0.484

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.503

Gnomad OTH

AF:

0.517

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

GnomAD4 genome

AF:

0.491

AC:

72136

AN:

146790

Hom.:

17707

Cov.:

AF XY:

0.492

AC XY:

35101

AN XY:

71320

show subpopulations

African (AFR)

AF:

0.446

AC:

17935

AN:

40226

American (AMR)

AF:

0.559

AC:

8290

AN:

14838

Ashkenazi Jewish (ASJ)

AF:

0.474

AC:

1639

AN:

3458

East Asian (EAS)

AF:

0.593

AC:

2994

AN:

5048

South Asian (SAS)

AF:

0.427

AC:

1996

AN:

4676

European-Finnish (FIN)

AF:

0.484

AC:

4088

AN:

8448

Middle Eastern (MID)

AF:

0.411

AC:

115

AN:

280

European-Non Finnish (NFE)

AF:

0.503

AC:

33647

AN:

66864

Other (OTH)

AF:

0.517

AC:

1058

AN:

2046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

1856

3712

5569

7425

9281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

638

1276

1914

2552

3190

<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:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.41

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over