rs10489595

chr1-117888980-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017686.4(GDAP2):c.954-1206A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0563 in 152,218 control chromosomes in the GnomAD database, including 586 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.056 (586 hom., cov: 32)
• Consequence: GDAP2 NM_017686.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GDAP2	NM_017686.4	c.954-1206A>G		intron_variant		ENST00000369443.10
GDAP2	NM_001135589.3	c.954-1206A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GDAP2	ENST00000369443.10	c.954-1206A>G		intron_variant		2	NM_017686.4	P1
GDAP2	ENST00000369442.3	c.954-1206A>G		intron_variant		1
GDAP2	ENST00000464026.1	n.232-1206A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0561 AC: 8538 AN: 152100 Hom.: 582 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0354

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0487

Gnomad SAS AF: 0.0959

Gnomad FIN AF: 0.00395

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00926

Gnomad OTH AF: 0.0360

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0563 AC: 8569 AN: 152218 Hom.: 586 Cov.: 32 AF XY: 0.0563 AC XY: 4192 AN XY: 74436

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.0353

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.0486

Gnomad4 SAS AF: 0.0954

Gnomad4 FIN AF: 0.00395

Gnomad4 NFE AF: 0.00926

Gnomad4 OTH AF: 0.0356

Alfa AF: 0.0391 Hom.: 59

Bravo AF: 0.0607

Asia WGS AF: 0.0860 AC: 298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.5
Dann	Benign	0.45

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

Other links and lift over

dbSNP: rs10489595; hg19: chr1-118431602;