rs3754127

Variant names:

• chr1-117928589-C-T
• rs3754127
• NM_017686.4:c.-68+859G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia, autosomal recessive 27

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017686.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDAP2	NM_017686.4	MANE Select	c.-68+859G>A		intron	N/A	NP_060156.1	Q9NXN4-1
	GDAP2	NM_001135589.3		c.-68+859G>A		intron	N/A	NP_001129061.1	Q9NXN4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GDAP2	ENST00000369443.10	TSL:2 MANE Select	c.-68+859G>A		intron	N/A	ENSP00000358451.4	Q9NXN4-1
	GDAP2	ENST00000369442.3	TSL:1	c.-68+859G>A		intron	N/A	ENSP00000358450.3	Q9NXN4-2
	GDAP2	ENST00000880444.1		c.-68+859G>A		intron	N/A	ENSP00000550503.1

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

African (AFR) AF: 0.132 AC: 5482 AN: 41546

American (AMR) AF: 0.384 AC: 5871 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1151 AN: 3472

East Asian (EAS) AF: 0.169 AC: 878 AN: 5188

South Asian (SAS) AF: 0.439 AC: 2116 AN: 4824

European-Finnish (FIN) AF: 0.420 AC: 4432 AN: 10550

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30936 AN: 67970

Other (OTH) AF: 0.350 AC: 738 AN: 2108

Alfa AF: 0.377 Hom.: 1966

Bravo AF: 0.327

Asia WGS AF: 0.287 AC: 1000 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.2
DANN	Benign	0.44
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3754127; hg19: chr1-118471212;