8-74350409-GGGA-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_018972.4(GDAP1):c.-51_-49del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,134,114 control chromosomes in the GnomAD database, including 128 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0028 (15 hom., cov: 34)
  • Exomes 𝑓: 0.0027 (113 hom.)
• Consequence: GDAP1 NM_018972.4 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.29

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 -16 ACMG points.

• BP6: Variant 8-74350409-GGGA-G is Benign according to our data. Variant chr8-74350409-GGGA-G is described in ClinVar as [Likely_benign]. Clinvar id is 363718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GDAP1	NM_018972.4	c.-51_-49del		5_prime_UTR_variant	1/6	ENST00000220822.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GDAP1	ENST00000220822.12	c.-51_-49del		5_prime_UTR_variant	1/6	1	NM_018972.4	P3

Frequencies

GnomAD3 genomes AF: 0.00283 AC: 431 AN: 152222 Hom.: 15 Cov.: 34

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0269

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00869 AC: 2092 AN: 240826 Hom.: 85 AF XY: 0.00621 AC XY: 815 AN XY: 131226

Gnomad AFR exome AF: 0.000640

Gnomad AMR exome AF: 0.0600

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000899

Gnomad OTH exome AF: 0.00367

GnomAD4 exome AF: 0.00270 AC: 2655 AN: 981774 Hom.: 113 AF XY: 0.00209 AC XY: 1064 AN XY: 508618

Gnomad4 AFR exome AF: 0.000448

Gnomad4 AMR exome AF: 0.0583

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000734

Gnomad4 OTH exome AF: 0.00145

GnomAD4 genome AF: 0.00284 AC: 432 AN: 152340 Hom.: 15 Cov.: 34 AF XY: 0.00297 AC XY: 221 AN XY: 74484

Gnomad4 AFR AF: 0.000337

Gnomad4 AMR AF: 0.0269

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00208 Hom.: 1

Bravo AF: 0.00592

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Charcot-Marie-Tooth with Vocal Cord Paresis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 25, 2016

- -

Charcot-Marie-Tooth, Intermediate Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs201803887; hg19: chr8-75262644;