chr16-28823518-C-G

Variant names:

• chr16-28823518-C-G
• rs1306642089
• NM_007245.4:c.259C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007245.4(ATXN2L):​c.259C>G​(p.His87Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000807 in 1,239,780 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H87Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: ATXN2L NM_007245.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.32
• Publications: 0 publications found

Genes affected

ATXN2L (HGNC:31326): (ataxin 2 like) This gene encodes an ataxin type 2 related protein of unknown function. This protein is a member of the spinocerebellar ataxia (SCAs) family, which is associated with a complex group of neurodegenerative disorders. Several alternatively spliced transcripts encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ENSG00000275807 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08234593).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007245.4. 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
	ATXN2L	NM_007245.4	MANE Select	c.259C>G	p.His87Asp	missense	Exon 1 of 22	NP_009176.2
	ATXN2L	NM_001387166.1		c.259C>G	p.His87Asp	missense	Exon 1 of 24	NP_001374095.1
	ATXN2L	NM_001387167.1		c.259C>G	p.His87Asp	missense	Exon 1 of 24	NP_001374096.1	Q8WWM7-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATXN2L	ENST00000336783.9	TSL:1 MANE Select	c.259C>G	p.His87Asp	missense	Exon 1 of 22	ENSP00000338718.4	Q8WWM7-1
	ATXN2L	ENST00000395547.6	TSL:1	c.259C>G	p.His87Asp	missense	Exon 1 of 24	ENSP00000378917.2	Q8WWM7-3
	ATXN2L	ENST00000564304.5	TSL:1	c.259C>G	p.His87Asp	missense	Exon 1 of 23	ENSP00000457613.1	H3BUF6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.07e-7 AC: 1 AN: 1239780 Hom.: 0 Cov.: 32 AF XY: 0.00000164 AC XY: 1 AN XY: 607994

African (AFR) AF: 0.00 AC: 0 AN: 24670

American (AMR) AF: 0.00 AC: 0 AN: 15588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20282

East Asian (EAS) AF: 0.00 AC: 0 AN: 27470

South Asian (SAS) AF: 0.00 AC: 0 AN: 59724

European-Finnish (FIN) AF: 0.0000334 AC: 1 AN: 29948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3552

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1008076

Other (OTH) AF: 0.00 AC: 0 AN: 50470

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	21
DANN	Benign	0.80
DEOGEN2	Benign	0.029	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.66
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		2.3
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.75	N
REVEL	Benign	0.058
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.79	T
Polyphen		0.0050	B
Vest4		0.24
MutPred		0.088		Loss of helix (P = 0.079)
MVP		0.30
MPC		0.69
ClinPred		0.34	T
GERP RS		1.6
PromoterAI		-0.0047	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.23
gMVP		0.23

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: rs1306642089; hg19: chr16-28834839;