Variant 1-117878162-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_017686.4(GDAP2):c.1303-10T>C variant causes a splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.00134 in 1,451,832 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0068 ( 9 hom., cov: 32)

Exomes 𝑓: 0.00070 ( 12 hom. )

Consequence

GDAP2
NM_017686.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0008056

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.28

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 Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 1-117878162-A-G is Benign according to our data. Variant chr1-117878162-A-G is described in ClinVar as [Benign]. Clinvar id is 3055753.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00679 (1034/152332) while in subpopulation AFR AF= 0.0234 (971/41576). AF 95% confidence interval is 0.0221. There are 9 homozygotes in gnomad4. There are 492 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDAP2	NM_017686.4 linkuse as main transcript	c.1303-10T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000369443.10	NP_060156.1
GDAP2	NM_001135589.3 linkuse as main transcript	c.1303-10T>C		splice_polypyrimidine_tract_variant, intron_variant			NP_001129061.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
GDAP2	ENST00000369443.10 linkuse as main transcript	c.1303-10T>C	splice_polypyrimidine_tract_variant, intron_variant	2	NM_017686.4	ENSP00000358451	P1	Q9NXN4-1
GDAP2	ENST00000369442.3 linkuse as main transcript	c.1303-10T>C	splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000358450		Q9NXN4-2
GDAP2	ENST00000491626.5 linkuse as main transcript	n.309-10T>C	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.00675

AC:

1028

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0233

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00196

AC:

412

AN:

210358

Hom.:

AF XY:

0.00145

AC XY:

166

AN XY:

114442

show subpopulations

Gnomad AFR exome

AF:

0.0262

Gnomad AMR exome

AF:

0.000800

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000644

Gnomad SAS exome

AF:

0.0000438

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000393

Gnomad OTH exome

AF:

0.000836

GnomAD4 exome

AF:

0.000702

AC:

912

AN:

1299500

Hom.:

Cov.:

AF XY:

0.000636

AC XY:

412

AN XY:

648196

show subpopulations

Gnomad4 AFR exome

AF:

0.0262

Gnomad4 AMR exome

AF:

0.000947

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000533

Gnomad4 SAS exome

AF:

0.0000559

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000242

Gnomad4 OTH exome

AF:

0.00155

GnomAD4 genome

AF:

0.00679

AC:

1034

AN:

152332

Hom.:

Cov.:

AF XY:

0.00660

AC XY:

492

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0234

Gnomad4 AMR

AF:

0.00320

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00487

Hom.:

Bravo

AF:

0.00789

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GDAP2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 01, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00081

dbscSNV1_RF

Benign

0.052

SpliceAI score (max)

0.010

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