NM_001009994.3:c.77_78delGCinsAT

Variant names:

• chr6-83853493-GC-AT
• NM_001009994.3:c.77_78delGCinsAT

Variant summary

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

The NM_001009994.3(RIPPLY2):​c.77_78delGCinsAT​(p.Arg26His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RIPPLY2 NM_001009994.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.300
• Publications: 0 publications found

Genes affected

RIPPLY2 (HGNC:21390): (ripply transcriptional repressor 2) This gene encodes a nuclear protein that belongs to a novel family of proteins required for vertebrate somitogenesis. Members of this family have a tetrapeptide WRPW motif that is required for interaction with the transcriptional repressor Groucho and a carboxy-terminal Ripply homology domain/Bowline-DSCR-Ledgerline conserved region required for transcriptional repression. Null mutant mice die soon after birth and display defects in axial skeleton segmentation due to defective somitogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

RIPPLY2 Gene-Disease associations (from GenCC):

• spondylocostal dysostosis 6, autosomal recessive

  Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal recessive spondylocostal dysostosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000287705 (HGNC:):

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009994.3. 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
	RIPPLY2	NM_001009994.3	MANE Select	c.77_78delGCinsAT	p.Arg26His	missense	N/A	NP_001009994.1	Q5TAB7-1
	RIPPLY2	NM_001400900.1		c.77_78delGCinsAT	p.Arg26His	missense	N/A	NP_001387829.1
	RIPPLY2-CYB5R4	NR_174604.1		n.134_135delGCinsAT		non_coding_transcript_exon	Exon 1 of 18

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPPLY2	ENST00000369689.6	TSL:1 MANE Select	c.77_78delGCinsAT	p.Arg26His	missense	N/A	ENSP00000358703.1	Q5TAB7-1
	ENSG00000287705	ENST00000656981.1		n.674_675delGCinsAT		non_coding_transcript_exon	Exon 1 of 1
	RIPPLY2	ENST00000369687.2	TSL:2	c.-281_-280delGCinsAT		upstream_gene	N/A	ENSP00000358701.1	Q5TAB7-2

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.30

Splicing

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

Other links and lift over

hg19: chr6-84563212;