10-73661450-G-A

Variant names:

• chr10-73661450-G-A
• rs10824026
• ENST00000606523.1:c.-103+2250C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000606523.1(SYNPO2L):​c.-103+2250C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 151,926 control chromosomes in the GnomAD database, including 39,016 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 0.69 (39016 hom., cov: 30)
• Consequence: SYNPO2L ENST00000606523.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 76 publications found

Genes affected

SYNPO2L (HGNC:23532): (synaptopodin 2 like) Predicted to enable actin binding activity. Predicted to be involved in several processes, including positive regulation of Rho protein signal transduction; positive regulation of stress fiber assembly; and sarcomere organization. Located in cell junction; cytosol; and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

SYNPO2L-AS1 (HGNC:55242): (SYNPO2L antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.845 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000606523.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNPO2L-AS1	NR_187518.1		n.269-6825G>A		intron	N/A
	SYNPO2L-AS1	NR_187519.1		n.269-6276G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNPO2L	ENST00000606523.1	TSL:4	c.-103+2250C>T		intron	N/A	ENSP00000475768.1
	SYNPO2L-AS1	ENST00000606726.2	TSL:4	n.468-6276G>A		intron	N/A
	SYNPO2L-AS1	ENST00000607450.3	TSL:5	n.460-6825G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104203 AN: 151808 Hom.: 39020 Cov.: 30

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.832

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.851

Gnomad OTH AF: 0.724

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

GnomAD4 genome AF: 0.686 AC: 104214 AN: 151926 Hom.: 39016 Cov.: 30 AF XY: 0.687 AC XY: 51013 AN XY: 74228

African (AFR) AF: 0.362 AC: 14989 AN: 41378

American (AMR) AF: 0.699 AC: 10660 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 2665 AN: 3470

East Asian (EAS) AF: 0.637 AC: 3276 AN: 5144

South Asian (SAS) AF: 0.723 AC: 3481 AN: 4816

European-Finnish (FIN) AF: 0.832 AC: 8798 AN: 10570

Middle Eastern (MID) AF: 0.741 AC: 218 AN: 294

European-Non Finnish (NFE) AF: 0.851 AC: 57850 AN: 67984

Other (OTH) AF: 0.723 AC: 1528 AN: 2112

Alfa AF: 0.790 Hom.: 172742

Bravo AF: 0.658

Asia WGS AF: 0.667 AC: 2315 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.0
DANN	Benign	0.68
PhyloP100		-1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10824026; hg19: chr10-75421208;