8-74350205-T-TAAA

Variant names:

• chr8-74350205-T-TAAA
• rs112601241
• ENST00000521872.2:n.109_111dupTTT

Variant summary

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

The ENST00000521872.2(ENSG00000253596):​n.109_111dupTTT 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 0.45 (14628 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-TAAA is Benign according to our data. Variant chr8-74350205-T-TAAA is described in ClinVar as [Benign]. Clinvar id is 1181979.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDAP1	NM_018972.4	c.-257_-256insAAA		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_-256insAAA		upstream_gene_variant		1	NM_018972.4	ENSP00000220822.7

Frequencies

GnomAD3 genomes AF: 0.445 AC: 65295 AN: 146702 Hom.: 14628 Cov.: 0

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.546

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.445 AC: 65298 AN: 146734 Hom.: 14628 Cov.: 0 AF XY: 0.447 AC XY: 31841 AN XY: 71306

African (AFR) AF: 0.374 AC: 15048 AN: 40188

American (AMR) AF: 0.402 AC: 5959 AN: 14832

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1767 AN: 3454

East Asian (EAS) AF: 0.401 AC: 2020 AN: 5042

South Asian (SAS) AF: 0.521 AC: 2436 AN: 4680

European-Finnish (FIN) AF: 0.506 AC: 4273 AN: 8450

Middle Eastern (MID) AF: 0.536 AC: 150 AN: 280

European-Non Finnish (NFE) AF: 0.482 AC: 32242 AN: 66854

Other (OTH) AF: 0.425 AC: 872 AN: 2050

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

Aug 18, 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;