ENST00000674710.1:c.694+17204C>T

Variant names:

• chr8-74380257-C-T
• rs6996971
• ENST00000674710.1:c.694+17204C>T

Variant summary

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

The ENST00000674710.1(GDAP1):​c.694+17204C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 151,916 control chromosomes in the GnomAD database, including 19,829 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 0.51 (19829 hom., cov: 32)
• Consequence: GDAP1 ENST00000674710.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 11 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000674710.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDAP1	NM_001362931.2		c.694+17204C>T		intron	N/A	NP_001349860.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDAP1	ENST00000674710.1		c.694+17204C>T		intron	N/A	ENSP00000502762.1
	GDAP1	ENST00000675999.1		c.694+17204C>T		intron	N/A	ENSP00000502572.1
	GDAP1	ENST00000676207.1		c.694+17204C>T		intron	N/A	ENSP00000502638.1

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77267 AN: 151796 Hom.: 19813 Cov.: 32

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.477

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

GnomAD4 genome AF: 0.509 AC: 77329 AN: 151916 Hom.: 19829 Cov.: 32 AF XY: 0.507 AC XY: 37650 AN XY: 74220

African (AFR) AF: 0.592 AC: 24507 AN: 41398

American (AMR) AF: 0.429 AC: 6540 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 1730 AN: 3470

East Asian (EAS) AF: 0.403 AC: 2085 AN: 5174

South Asian (SAS) AF: 0.510 AC: 2457 AN: 4814

European-Finnish (FIN) AF: 0.518 AC: 5450 AN: 10528

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.483 AC: 32851 AN: 67968

Other (OTH) AF: 0.477 AC: 1004 AN: 2104

Alfa AF: 0.485 Hom.: 56537

Bravo AF: 0.505

Asia WGS AF: 0.465 AC: 1617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.35
DANN	Benign	0.55
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs6996971; hg19: chr8-75292492;