Variant chr1-117883580-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017686.4(GDAP2):c.1155G>T(p.Glu385Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000875 in 1,599,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000090 ( 0 hom. )

Consequence

GDAP2
NM_017686.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0670

Variant links:

Genes affected

GDAP2 (HGNC:18010): (ganglioside induced differentiation associated protein 2) Predicted to act upstream of or within response to retinoic acid. Located in lysosomal membrane. Implicated in autosomal recessive spinocerebellar ataxia 27. [provided by Alliance of Genome Resources, Apr 2022]

GDAP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07940373).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDAP2	NM_017686.4 linkuse as main transcript	c.1155G>T	p.Glu385Asp	missense_variant	11/14	ENST00000369443.10	NP_060156.1
GDAP2	NM_001135589.3 linkuse as main transcript	c.1155G>T	p.Glu385Asp	missense_variant	11/13		NP_001129061.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDAP2	ENST00000369443.10 linkuse as main transcript	c.1155G>T	p.Glu385Asp	missense_variant	11/14	2	NM_017686.4	ENSP00000358451	P1	Q9NXN4-1
GDAP2	ENST00000369442.3 linkuse as main transcript	c.1155G>T	p.Glu385Asp	missense_variant	11/13	1		ENSP00000358450		Q9NXN4-2
GDAP2	ENST00000464026.1 linkuse as main transcript	n.433G>T		non_coding_transcript_exon_variant	5/5	2
GDAP2	ENST00000491626.5 linkuse as main transcript	n.161G>T		non_coding_transcript_exon_variant	3/7	3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

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:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250586

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135448

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000898

AC:

AN:

1447556

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

720962

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000273

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

The c.1155G>T (p.E385D) alteration is located in exon 11 (coding exon 10) of the GDAP2 gene. This alteration results from a G to T substitution at nucleotide position 1155, causing the glutamic acid (E) at amino acid position 385 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.42

CADD

Benign

1.4

DANN

Benign

0.30

DEOGEN2

Benign

0.023

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.76

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.023

MetaRNN

Benign

0.079

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.38

N;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

0.57

N;N

REVEL

Benign

0.13

Sift

Benign

1.0

T;T

Sift4G

Benign

0.79

T;T

Polyphen

0.020

B;B

Vest4

0.46

MutPred

0.55

Loss of ubiquitination at K384 (P = 0.1151);Loss of ubiquitination at K384 (P = 0.1151);

MVP

0.39

MPC

0.20

ClinPred

0.041

GERP RS

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.51

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over