8-74382740-T-G

Variant names:

• chr8-74382740-T-G
• rs4471028
• ENST00000674710.1:c.694+19687T>G

Variant summary

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

The NM_001362931.2(GDAP1):​c.694+19687T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,892 control chromosomes in the GnomAD database, including 10,487 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 0.36 (10487 hom., cov: 31)
• Consequence: GDAP1 NM_001362931.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210
• Publications: 12 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001362931.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDAP1	NM_001362931.2		c.694+19687T>G		intron	N/A	NP_001349860.1	A0A6Q8PH97

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDAP1	ENST00000674710.1		c.694+19687T>G		intron	N/A	ENSP00000502762.1	A0A6Q8PHN7
	GDAP1	ENST00000675999.1		c.694+19687T>G		intron	N/A	ENSP00000502572.1	A0A6Q8PH88
	GDAP1	ENST00000676207.1		c.694+19687T>G		intron	N/A	ENSP00000502638.1	A0A6Q8PH97

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55238 AN: 151774 Hom.: 10487 Cov.: 31

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.350

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

GnomAD4 genome AF: 0.364 AC: 55259 AN: 151892 Hom.: 10487 Cov.: 31 AF XY: 0.366 AC XY: 27156 AN XY: 74224

African (AFR) AF: 0.252 AC: 10463 AN: 41472

American (AMR) AF: 0.333 AC: 5093 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1589 AN: 3464

East Asian (EAS) AF: 0.285 AC: 1468 AN: 5152

South Asian (SAS) AF: 0.455 AC: 2190 AN: 4810

European-Finnish (FIN) AF: 0.436 AC: 4590 AN: 10524

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.420 AC: 28533 AN: 67874

Other (OTH) AF: 0.351 AC: 742 AN: 2114

Alfa AF: 0.401 Hom.: 52968

Bravo AF: 0.349

Asia WGS AF: 0.357 AC: 1232 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.6
DANN	Benign	0.69
PhyloP100		-0.021

Splicing

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

Other links and lift over

dbSNP: rs4471028; hg19: chr8-75294975;