ENST00000675944.1:c.-240_-237dupAAAA

Variant names:

• chr8-74350205-T-TAAAA
• rs112601241
• ENST00000675944.1:c.-240_-237dupAAAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000675944.1(GDAP1):​c.-240_-237dupAAAA 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 0.046 (502 hom., cov: 0)
• Consequence: GDAP1 ENST00000675944.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.410
• Publications: 1 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

ENSG00000253596 (HGNC:):

ACMG classification

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

• BP6: Variant 8-74350205-T-TAAAA is Benign according to our data. Variant chr8-74350205-T-TAAAA is described in ClinVar as Benign. ClinVar VariationId is 1237203.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 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

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

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDAP1	ENST00000675944.1		c.-240_-237dupAAAA		5_prime_UTR	Exon 1 of 6	ENSP00000502673.1	Q8TB36-2
	GDAP1	ENST00000674806.1		c.-218_-215dupAAAA		5_prime_UTR	Exon 1 of 6	ENSP00000502637.1	B4DIH2
	GDAP1	ENST00000674612.1		c.-17-9924_-17-9921dupAAAA		intron	N/A	ENSP00000501864.1	B4DIH2

Frequencies

GnomAD3 genomes AF: 0.0459 AC: 6744 AN: 146812 Hom.: 503 Cov.: 0

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0218

Gnomad ASJ AF: 0.00289

Gnomad EAS AF: 0.00355

Gnomad SAS AF: 0.00170

Gnomad FIN AF: 0.00118

Gnomad MID AF: 0.0261

Gnomad NFE AF: 0.00121

Gnomad OTH AF: 0.0369

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

GnomAD4 genome AF: 0.0460 AC: 6748 AN: 146844 Hom.: 502 Cov.: 0 AF XY: 0.0434 AC XY: 3098 AN XY: 71360

African (AFR) AF: 0.154 AC: 6214 AN: 40224

American (AMR) AF: 0.0218 AC: 324 AN: 14852

Ashkenazi Jewish (ASJ) AF: 0.00289 AC: 10 AN: 3458

East Asian (EAS) AF: 0.00356 AC: 18 AN: 5050

South Asian (SAS) AF: 0.00171 AC: 8 AN: 4680

European-Finnish (FIN) AF: 0.00118 AC: 10 AN: 8472

Middle Eastern (MID) AF: 0.0286 AC: 8 AN: 280

European-Non Finnish (NFE) AF: 0.00121 AC: 81 AN: 66870

Other (OTH) AF: 0.0365 AC: 75 AN: 2052

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.41

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.

Other links and lift over

dbSNP: rs112601241; hg19: chr8-75262440;