chr1-117888980-T-C

Variant names:

• chr1-117888980-T-C
• rs10489595
• NM_017686.4:c.954-1206A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 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.954-1206A>G		intron	N/A	NP_060156.1	Q9NXN4-1
	GDAP2	NM_001135589.3		c.954-1206A>G		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.954-1206A>G		intron	N/A	ENSP00000358451.4	Q9NXN4-1
	GDAP2	ENST00000369442.3	TSL:1	c.954-1206A>G		intron	N/A	ENSP00000358450.3	Q9NXN4-2
	GDAP2	ENST00000880444.1		c.954-1206A>G		intron	N/A	ENSP00000550503.1

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

African (AFR) AF: 0.158 AC: 6558 AN: 41520

American (AMR) AF: 0.0353 AC: 539 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.0486 AC: 252 AN: 5182

South Asian (SAS) AF: 0.0954 AC: 460 AN: 4824

European-Finnish (FIN) AF: 0.00395 AC: 42 AN: 10624

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00926 AC: 630 AN: 68004

Other (OTH) AF: 0.0356 AC: 75 AN: 2106

Alfa AF: 0.0472 Hom.: 78

Bravo AF: 0.0607

Asia WGS AF: 0.0860 AC: 298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.45
PhyloP100		0.0010
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: rs10489595; hg19: chr1-118431602;