rs772340154

Variant names:

• chr16-4802506-CCGCTGGCCCGCG-C
• rs772340154
• NM_024589.3:c.45+9_45+20delCGCGGGCCAGCG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP5_Moderate

The NM_024589.3(ROGDI):​c.45+9_45+20delCGCGGGCCAGCG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000355 in 1,211,368 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: ROGDI NM_024589.3 intron
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:2
• Conservation: PhyloP100: 0.380
• Publications: 2 publications found

Genes affected

ROGDI (HGNC:29478): (rogdi atypical leucine zipper) Involved in brain development; neurogenesis; and odontogenesis of dentin-containing tooth. Located in nuclear envelope. Implicated in Kohlschutter-Tonz syndrome. [provided by Alliance of Genome Resources, Apr 2022]

ROGDI Gene-Disease associations (from GenCC):

• amelocerebrohypohidrotic syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PP5: Variant 16-4802506-CCGCTGGCCCGCG-C is Pathogenic according to our data. Variant chr16-4802506-CCGCTGGCCCGCG-C is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 41467.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024589.3. 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
	ROGDI	NM_024589.3	MANE Select	c.45+9_45+20delCGCGGGCCAGCG		intron	N/A	NP_078865.1
	ROGDI	NR_046480.2		n.107+9_107+20delCGCGGGCCAGCG		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ROGDI	ENST00000322048.12	TSL:1 MANE Select	c.45+9_45+20delCGCGGGCCAGCG		intron	N/A	ENSP00000322832.6
	ROGDI	ENST00000907806.1		c.45+9_45+20delCGCGGGCCAGCG		intron	N/A	ENSP00000577865.1
	ROGDI	ENST00000912071.1		c.45+9_45+20delCGCGGGCCAGCG		intron	N/A	ENSP00000582130.1

Frequencies

GnomAD3 genomes AF: 0.0000465 AC: 7 AN: 150610 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000104

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 1408 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000339 AC: 36 AN: 1060758 Hom.: 0 AF XY: 0.0000337 AC XY: 17 AN XY: 504784

African (AFR) AF: 0.00 AC: 0 AN: 21666

American (AMR) AF: 0.00 AC: 0 AN: 7246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12690

East Asian (EAS) AF: 0.00 AC: 0 AN: 23518

South Asian (SAS) AF: 0.00 AC: 0 AN: 20714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20642

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2814

European-Non Finnish (NFE) AF: 0.0000374 AC: 34 AN: 910014

Other (OTH) AF: 0.0000482 AC: 2 AN: 41454

GnomAD4 genome AF: 0.0000465 AC: 7 AN: 150610 Hom.: 0 Cov.: 33 AF XY: 0.0000408 AC XY: 3 AN XY: 73512

African (AFR) AF: 0.00 AC: 0 AN: 41248

American (AMR) AF: 0.00 AC: 0 AN: 15098

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000104 AC: 7 AN: 67554

Other (OTH) AF: 0.00 AC: 0 AN: 2070

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000302

ClinVar

ClinVar submissions as Germline

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
2	-	-	Amelocerebrohypohidrotic syndrome (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.38
Mutation Taster		=42/58	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs772340154; hg19: chr16-4852507;