1-243344297-CAA-CA

Variant summary

Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1 PM2 PP5_Very_Strong

The NM_006642.5(SDCCAG8):c.1444del(p.Thr482LeufsTer12) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,486 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: SDCCAG8 NM_006642.5 frameshift
• Clinical Significance: Pathogenic criteria provided, multiple submitters, no conflicts P:3
• Conservation: PhyloP100: 1.22

Genes affected

SDCCAG8 (HGNC:10671): (SHH signaling and ciliogenesis regulator SDCCAG8) This gene encodes a centrosome associated protein. This protein may be involved in organizing the centrosome during interphase and mitosis. Mutations in this gene are associated with retinal-renal ciliopathy. [provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Pathogenic. Variant got 18 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-243344297-CA-C is Pathogenic according to our data. Variant chr1-243344297-CA-C is described in ClinVar as [Pathogenic]. Clinvar id is 156529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-243344297-CA-C is described in Lovd as [Likely_pathogenic]. Variant chr1-243344297-CA-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SDCCAG8	NM_006642.5	c.1444del	p.Thr482LeufsTer12	frameshift_variant	12/18	ENST00000366541.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SDCCAG8	ENST00000366541.8	c.1444del	p.Thr482LeufsTer12	frameshift_variant	12/18	1	NM_006642.5	P1
SDCCAG8	ENST00000435549.1	c.784del	p.Thr262LeufsTer12	frameshift_variant	7/11	1
SDCCAG8	ENST00000493334.1	n.411del		non_coding_transcript_exon_variant	3/5	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000159 AC: 4 AN: 251276 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135824

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000123 AC: 18 AN: 1461486 Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14 AN XY: 727088

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000209

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Senior-Loken syndrome 7;C3889474:Bardet-Biedl syndrome 16 Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Invitae

Jul 19, 2023

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 156529). This premature translational stop signal has been observed in individual(s) with ciliopathy features including renal disease and retinal dystrophy (PMID: 20835237, 22626039). This variant is present in population databases (rs773794973, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Thr482Leufs*12) in the SDCCAG8 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SDCCAG8 are known to be pathogenic (PMID: 20835237, 22190896). -

not provided Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Feb 21, 2017

- -

Bardet-Biedl syndrome 16 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 01, 2012

- -

Computational scores

Source: dbNSFP v4.3

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: rs587777847; hg19: chr1-243507599;