8-74350205-TA-TAA

Variant names:

• chr8-74350205-T-TA
• rs112601241
• ENST00000521872.2:n.111dupT

Variant summary

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

The ENST00000521872.2(ENSG00000253596):​n.111dupT variant causes a non coding transcript exon 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: ENSG00000253596 ENST00000521872.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.410
• Publications: 1 publications found

Genes affected

ENSG00000253596 (HGNC:):

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: 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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDAP1	NM_018972.4	c.-257_-256insA		upstream_gene_variant		ENST00000220822.12	NP_061845.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDAP1	ENST00000220822.12	c.-257_-256insA		upstream_gene_variant		1	NM_018972.4	ENSP00000220822.7

Frequencies

GnomAD3 genomes AF: 0.491 AC: 72117 AN: 146758 Hom.: 17699 Cov.: 0

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.: 0 AF XY: 0.492 AC XY: 35101 AN XY: 71320

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

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 14, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs112601241; hg19: chr8-75262440; COSMIC: COSV55186763;