rs7828201

chr8-74350563-C-Gchr8-74350563-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS1

The NM_018972.4(GDAP1):c.102C>G(p.Ser34=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,601,090 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00074 (1 hom., cov: 34)
  • Exomes 𝑓: 0.0012 (29 hom.)
• Consequence: GDAP1 NM_018972.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0260

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 8-74350563-C-G is Benign according to our data. Variant chr8-74350563-C-G is described in ClinVar as [Benign]. Clinvar id is 467755.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.026 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000735 (112/152376) while in subpopulation SAS AF= 0.0228 (110/4834). AF 95% confidence interval is 0.0193. There are 1 homozygotes in gnomad4. There are 88 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GDAP1	NM_018972.4	c.102C>G	p.Ser34=	synonymous_variant	1/6	ENST00000220822.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GDAP1	ENST00000220822.12	c.102C>G	p.Ser34=	synonymous_variant	1/6	1	NM_018972.4	P3

Frequencies

GnomAD3 genomes AF: 0.000736 AC: 112 AN: 152258 Hom.: 1 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0227

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000955

GnomAD4 exome AF: 0.00118 AC: 1715 AN: 1448714 Hom.: 29 Cov.: 28 AF XY: 0.00174 AC XY: 1259 AN XY: 721580

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0189

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000454

Gnomad4 OTH exome AF: 0.00135

GnomAD4 genome AF: 0.000735 AC: 112 AN: 152376 Hom.: 1 Cov.: 34 AF XY: 0.00118 AC XY: 88 AN XY: 74506

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0228

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.0000725 Hom.: 0

Bravo AF: 0.0000907

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Charcot-Marie-Tooth disease type 4A Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 04, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	13

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7828201; hg19: chr8-75262798;