1-243435368-A-G

Variant names:

• chr1-243435368-A-G
• rs2039839
• NM_006642.5:c.1985+8810A>G

Variant summary

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

The NM_006642.5(SDCCAG8):​c.1985+8810A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 152,002 control chromosomes in the GnomAD database, including 20,787 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 0.50 (20787 hom., cov: 32)
• Consequence: SDCCAG8 NM_006642.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.690
• Publications: 5 publications found

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]

SDCCAG8 Gene-Disease associations (from GenCC):

• Senior-Loken syndrome 7

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• Bardet-Biedl syndrome 16

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Senior-Loken syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SDCCAG8	NM_006642.5	c.1985+8810A>G		intron_variant	Intron 16 of 17	ENST00000366541.8	NP_006633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SDCCAG8	ENST00000366541.8	c.1985+8810A>G		intron_variant	Intron 16 of 17	1	NM_006642.5	ENSP00000355499.3
SDCCAG8	ENST00000435549.1	c.1088+8810A>G		intron_variant	Intron 9 of 10	1		ENSP00000410200.1
SDCCAG8	ENST00000463042.1	n.192+8810A>G		intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76470 AN: 151884 Hom.: 20782 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.622

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.503 AC: 76487 AN: 152002 Hom.: 20787 Cov.: 32 AF XY: 0.503 AC XY: 37382 AN XY: 74282

African (AFR) AF: 0.295 AC: 12239 AN: 41438

American (AMR) AF: 0.622 AC: 9509 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1977 AN: 3466

East Asian (EAS) AF: 0.782 AC: 4044 AN: 5174

South Asian (SAS) AF: 0.438 AC: 2110 AN: 4818

European-Finnish (FIN) AF: 0.559 AC: 5901 AN: 10556

Middle Eastern (MID) AF: 0.619 AC: 182 AN: 294

European-Non Finnish (NFE) AF: 0.573 AC: 38970 AN: 67962

Other (OTH) AF: 0.543 AC: 1141 AN: 2102

Alfa AF: 0.546 Hom.: 12620

Bravo AF: 0.499

Asia WGS AF: 0.591 AC: 2055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.85
PhyloP100		0.69
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: rs2039839; hg19: chr1-243598670;