rs6472842

Variant names:

• chr8-74366222-A-G
• rs6472842
• NM_018972.4:c.*1855A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-74366222-A-G
• chr8-74366222-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018972.4(GDAP1):​c.*1855A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 453,828 control chromosomes in the GnomAD database, including 20,947 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7054 hom., cov: 32)
  • Exomes 𝑓: 0.29 (13893 hom.)
• Consequence: GDAP1 NM_018972.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.23
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 8-74366222-A-G is Benign according to our data. Variant chr8-74366222-A-G is described in ClinVar as Benign. ClinVar VariationId is 363752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018972.4. 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_018972.4	MANE Select	c.*1855A>G		3_prime_UTR	Exon 6 of 6	NP_061845.2	Q8TB36-1
	GDAP1	NM_001362930.2		c.*1855A>G		3_prime_UTR	Exon 5 of 5	NP_001349859.1	A0A6Q8PEZ4
	GDAP1	NM_001040875.4		c.*1855A>G		3_prime_UTR	Exon 6 of 6	NP_001035808.1	Q8TB36-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDAP1	ENST00000220822.12	TSL:1 MANE Select	c.*1855A>G		3_prime_UTR	Exon 6 of 6	ENSP00000220822.7	Q8TB36-1
	GDAP1	ENST00000675463.1		c.*1855A>G		3_prime_UTR	Exon 7 of 7	ENSP00000502327.1	A0A6Q8PGS2
	GDAP1	ENST00000676112.1		c.*1855A>G		3_prime_UTR	Exon 7 of 7	ENSP00000502295.1	A0A6Q8PGL3

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45577 AN: 151950 Hom.: 7053 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.312

GnomAD2 exomes AF: 0.283 AC: 38461 AN: 135968 AF XY: 0.283

Gnomad AFR exome AF: 0.250

Gnomad AMR exome AF: 0.202

Gnomad ASJ exome AF: 0.282

Gnomad EAS exome AF: 0.330

Gnomad FIN exome AF: 0.342

Gnomad NFE exome AF: 0.335

Gnomad OTH exome AF: 0.316

GnomAD4 exome AF: 0.294 AC: 88866 AN: 301760 Hom.: 13893 Cov.: 0 AF XY: 0.288 AC XY: 49504 AN XY: 171930

African (AFR) AF: 0.256 AC: 2192 AN: 8548

American (AMR) AF: 0.203 AC: 5524 AN: 27206

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 3123 AN: 10776

East Asian (EAS) AF: 0.325 AC: 2995 AN: 9210

South Asian (SAS) AF: 0.210 AC: 12483 AN: 59388

European-Finnish (FIN) AF: 0.339 AC: 4340 AN: 12784

Middle Eastern (MID) AF: 0.267 AC: 307 AN: 1148

European-Non Finnish (NFE) AF: 0.338 AC: 53574 AN: 158670

Other (OTH) AF: 0.308 AC: 4328 AN: 14030

GnomAD4 genome AF: 0.300 AC: 45616 AN: 152068 Hom.: 7054 Cov.: 32 AF XY: 0.299 AC XY: 22201 AN XY: 74310

African (AFR) AF: 0.256 AC: 10626 AN: 41488

American (AMR) AF: 0.254 AC: 3882 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1066 AN: 3470

East Asian (EAS) AF: 0.312 AC: 1614 AN: 5168

South Asian (SAS) AF: 0.212 AC: 1021 AN: 4816

European-Finnish (FIN) AF: 0.333 AC: 3512 AN: 10562

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.336 AC: 22866 AN: 67964

Other (OTH) AF: 0.314 AC: 665 AN: 2116

Alfa AF: 0.311 Hom.: 4386

Bravo AF: 0.293

Asia WGS AF: 0.265 AC: 922 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Charcot-Marie-Tooth disease recessive intermediate A (1)
-	-	1	Charcot-Marie-Tooth disease, axonal, with vocal cord paresis, autosomal recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.55
DANN	Benign	0.38
PhyloP100		-1.2
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: rs6472842; hg19: chr8-75278457; COSMIC: COSV55185002; COSMIC: COSV55185002;