Variant 1-117896840-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_017686.4(GDAP2):c.946C>T(p.Gln316Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000671 in 1,609,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000067 ( 0 hom. )

Consequence

GDAP2
NM_017686.4 stop_gained

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 9.13

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 Pathogenic. Variant got 12 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 1-117896840-G-A is Pathogenic according to our data. Variant chr1-117896840-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 624618.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-117896840-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDAP2	NM_017686.4 linkuse as main transcript	c.946C>T	p.Gln316Ter	stop_gained	8/14	ENST00000369443.10	NP_060156.1
GDAP2	NM_001135589.3 linkuse as main transcript	c.946C>T	p.Gln316Ter	stop_gained	8/13		NP_001129061.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDAP2	ENST00000369443.10 linkuse as main transcript	c.946C>T	p.Gln316Ter	stop_gained	8/14	2	NM_017686.4	ENSP00000358451	P1	Q9NXN4-1
GDAP2	ENST00000369442.3 linkuse as main transcript	c.946C>T	p.Gln316Ter	stop_gained	8/13	1		ENSP00000358450		Q9NXN4-2
GDAP2	ENST00000464026.1 linkuse as main transcript	n.224C>T		non_coding_transcript_exon_variant	2/5	2
GDAP2	ENST00000493555.5 linkuse as main transcript	n.796C>T		non_coding_transcript_exon_variant	7/7	5

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000117

AC:

AN:

247516

Hom.:

AF XY:

0.0000897

AC XY:

AN XY:

133726

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00233

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000356

Gnomad OTH exome

AF:

0.000333

GnomAD4 exome

AF:

0.0000673

AC:

AN:

1457242

Hom.:

Cov.:

AF XY:

0.0000621

AC XY:

AN XY:

724776

show subpopulations

Gnomad4 AFR exome

AF:

0.0000602

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00247

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152108

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000384

Hom.:

Bravo

AF:

0.000117

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000596

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Spinocerebellar ataxia, autosomal recessive 27

Pathogenic:2

Pathogenic, no assertion criteria provided	literature only	OMIM	Mar 28, 2019	- -
Pathogenic, criteria provided, single submitter	clinical testing	Centogene AG - the Rare Disease Company	Sep 24, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.58

BayesDel_noAF

Pathogenic

0.65

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

1.2

Eigen_PC

Pathogenic

1.0

FATHMM_MKL

Pathogenic

1.0

MutationTaster

Benign

1.0

A;A

Vest4

0.25

GERP RS

5.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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