chr8-74350371-CCT-C

Position:

• chr8-74350371-CCT-C

Variant summary

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

The ENST00000675944.1(GDAP1):​c.-88+8_-88+9del variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 871,388 control chromosomes in the GnomAD database, including 12 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (5 hom., cov: 34)
  • Exomes 𝑓: 0.00064 (7 hom.)
• Consequence: GDAP1 ENST00000675944.1 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.154

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 8-74350371-CCT-C is Benign according to our data. Variant chr8-74350371-CCT-C is described in ClinVar as [Benign]. Clinvar id is 1168527.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00422 (643/152296) while in subpopulation AFR AF= 0.0133 (551/41568). AF 95% confidence interval is 0.0123. There are 5 homozygotes in gnomad4. There are 297 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDAP1	NM_018972.4			upstream_gene_variant		ENST00000220822.12	NP_061845.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDAP1	ENST00000220822.12			upstream_gene_variant		1	NM_018972.4	ENSP00000220822	P3

Frequencies

GnomAD3 genomes AF: 0.00423 AC: 643 AN: 152178 Hom.: 5 Cov.: 34

Gnomad AFR AF: 0.0133

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00121 AC: 269 AN: 222410 Hom.: 4 AF XY: 0.000947 AC XY: 116 AN XY: 122466

Gnomad AFR exome AF: 0.0137

Gnomad AMR exome AF: 0.00153

Gnomad ASJ exome AF: 0.000933

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000103

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000156

Gnomad OTH exome AF: 0.00124

GnomAD4 exome AF: 0.000638 AC: 459 AN: 719092 Hom.: 7 AF XY: 0.000507 AC XY: 195 AN XY: 384976

Gnomad4 AFR exome AF: 0.0126

Gnomad4 AMR exome AF: 0.00183

Gnomad4 ASJ exome AF: 0.000790

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000990

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000100

Gnomad4 OTH exome AF: 0.00163

GnomAD4 genome AF: 0.00422 AC: 643 AN: 152296 Hom.: 5 Cov.: 34 AF XY: 0.00399 AC XY: 297 AN XY: 74470

Gnomad4 AFR AF: 0.0133

Gnomad4 AMR AF: 0.00431

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00230 Hom.: 0

Bravo AF: 0.00520

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Charcot-Marie-Tooth disease type 4A Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 30, 2023

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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: rs577136201; hg19: chr8-75262606;