1-117928589-C-T

Position:

• chr1-117928589-C-T

Variant summary

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

The NM_017686.4(GDAP2):​c.-68+859G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,152 control chromosomes in the GnomAD database, including 10,653 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 0.34 (10653 hom., cov: 33)
• Consequence: GDAP2 NM_017686.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDAP2	NM_017686.4	c.-68+859G>A		intron_variant		ENST00000369443.10	NP_060156.1
GDAP2	NM_001135589.3	c.-68+859G>A		intron_variant			NP_001129061.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDAP2	ENST00000369443.10	c.-68+859G>A		intron_variant		2	NM_017686.4	ENSP00000358451	P1
GDAP2	ENST00000369442.3	c.-68+859G>A		intron_variant		1		ENSP00000358450
GDAP2	ENST00000494224.1	n.113+859G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52330 AN: 152034 Hom.: 10654 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.344 AC: 52332 AN: 152152 Hom.: 10653 Cov.: 33 AF XY: 0.344 AC XY: 25596 AN XY: 74356

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.439

Gnomad4 FIN AF: 0.420

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.350

Alfa AF: 0.385 Hom.: 1963

Bravo AF: 0.327

Asia WGS AF: 0.287 AC: 1000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.2
DANN	Benign	0.44

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: rs3754127; hg19: chr1-118471212;