Variant 1-117896981-C-T 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.805G>A(p.Glu269Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GDAP2
NM_017686.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.53

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:

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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=0.16140339).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDAP2	NM_017686.4 linkuse as main transcript	c.805G>A	p.Glu269Lys	missense_variant	8/14	ENST00000369443.10	NP_060156.1
GDAP2	NM_001135589.3 linkuse as main transcript	c.805G>A	p.Glu269Lys	missense_variant	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.805G>A	p.Glu269Lys	missense_variant	8/14	2	NM_017686.4	ENSP00000358451	P1	Q9NXN4-1
GDAP2	ENST00000369442.3 linkuse as main transcript	c.805G>A	p.Glu269Lys	missense_variant	8/13	1		ENSP00000358450		Q9NXN4-2
GDAP2	ENST00000464026.1 linkuse as main transcript	n.83G>A		non_coding_transcript_exon_variant	2/5	2
GDAP2	ENST00000493555.5 linkuse as main transcript	n.655G>A		non_coding_transcript_exon_variant	7/7	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.91e-7

AC:

AN:

1447846

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

720410

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.05e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 10, 2023

The c.805G>A (p.E269K) alteration is located in exon 8 (coding exon 7) of the GDAP2 gene. This alteration results from a G to A substitution at nucleotide position 805, causing the glutamic acid (E) at amino acid position 269 to be replaced by a lysine (K). 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

0.10

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.039

T;.

Eigen

Benign

0.074

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;L

MutationTaster

Benign

0.96

D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.088

Sift

Benign

0.13

T;T

Sift4G

Benign

0.80

T;T

Polyphen

0.020

B;P

Vest4

0.35

MutPred

0.38

Gain of ubiquitination at E269 (P = 0.0051);Gain of ubiquitination at E269 (P = 0.0051);

MVP

0.48

MPC

0.25

ClinPred

0.58

GERP RS

5.7

Varity_R

0.046

gMVP

0.32

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over