rs9298238

Variant names:

• chr8-74355383-A-G
• rs9298238
• NM_018972.4:c.310+3917A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018972.4(GDAP1):​c.310+3917A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,086 control chromosomes in the GnomAD database, including 14,367 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (14367 hom., cov: 33)
• Consequence: GDAP1 NM_018972.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168
• Publications: 1 publications found

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]

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDAP1	NM_018972.4	c.310+3917A>G		intron_variant	Intron 2 of 5	ENST00000220822.12	NP_061845.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDAP1	ENST00000220822.12	c.310+3917A>G		intron_variant	Intron 2 of 5	1	NM_018972.4	ENSP00000220822.7

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65584 AN: 151968 Hom.: 14366 Cov.: 33

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.475

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.431 AC: 65610 AN: 152086 Hom.: 14367 Cov.: 33 AF XY: 0.434 AC XY: 32233 AN XY: 74342

African (AFR) AF: 0.338 AC: 14013 AN: 41488

American (AMR) AF: 0.395 AC: 6035 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 1755 AN: 3466

East Asian (EAS) AF: 0.403 AC: 2081 AN: 5168

South Asian (SAS) AF: 0.516 AC: 2489 AN: 4828

European-Finnish (FIN) AF: 0.509 AC: 5383 AN: 10566

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.475 AC: 32278 AN: 67966

Other (OTH) AF: 0.420 AC: 887 AN: 2112

Alfa AF: 0.451 Hom.: 2040

Bravo AF: 0.419

Asia WGS AF: 0.453 AC: 1573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.5
DANN	Benign	0.71
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9298238; hg19: chr8-75267618;