8-74350205-TA-TAAAAA

Variant names:

• chr8-74350205-T-TAAAA
• rs112601241
• ENST00000521872.2:n.108_111dupTTTT

Variant summary

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

The ENST00000521872.2(ENSG00000253596):​n.108_111dupTTTT 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 0.046 (502 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-TAAAA is Benign according to our data. Variant chr8-74350205-T-TAAAA is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

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

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 02, 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

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;