8-74350205-T-TAA

Position:

• chr8-74350205-T-TAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000675944.1(GDAP1):​c.-238_-237dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0086 (11 hom., cov: 0)
• Consequence: GDAP1 ENST00000675944.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.410

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 8-74350205-T-TAA is Benign according to our data. Variant chr8-74350205-T-TAA is described in ClinVar as [Likely_benign]. Clinvar id is 1202471.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0086 (1262/146788) while in subpopulation SAS AF= 0.0272 (127/4676). AF 95% confidence interval is 0.0233. There are 11 homozygotes in gnomad4. There are 625 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 11 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDAP1	ENST00000674806.1	c.-216_-215dup		5_prime_UTR_variant	1/6			ENSP00000502637
GDAP1	ENST00000675944.1	c.-238_-237dup		5_prime_UTR_variant	1/6			ENSP00000502673
GDAP1	ENST00000674612.1	c.-17-9922_-17-9921dup		intron_variant				ENSP00000501864

Frequencies

GnomAD3 genomes AF: 0.00859 AC: 1260 AN: 146756 Hom.: 11 Cov.: 0

Gnomad AFR AF: 0.00314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0119

Gnomad ASJ AF: 0.00868

Gnomad EAS AF: 0.000790

Gnomad SAS AF: 0.0270

Gnomad FIN AF: 0.00615

Gnomad MID AF: 0.0131

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.0113

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

GnomAD4 genome AF: 0.00860 AC: 1262 AN: 146788 Hom.: 11 Cov.: 0 AF XY: 0.00876 AC XY: 625 AN XY: 71332

Gnomad4 AFR AF: 0.00320

Gnomad4 AMR AF: 0.0119

Gnomad4 ASJ AF: 0.00868

Gnomad4 EAS AF: 0.000792

Gnomad4 SAS AF: 0.0272

Gnomad4 FIN AF: 0.00615

Gnomad4 NFE AF: 0.0107

Gnomad4 OTH AF: 0.0112

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs112601241; hg19: chr8-75262440;