Variant 6-83853428-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001009994.3(RIPPLY2):c.12G>A(p.Ala4Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,542,804 control chromosomes in the GnomAD database, including 21,502 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 8046 hom., cov: 33)

Exomes 𝑓: 0.10 ( 13456 hom. )

Consequence

RIPPLY2
NM_001009994.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.860

Variant links:

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 links:

ENSG00000287705 (HGNC:):

ENSG00000287705 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 6-83853428-G-A is Benign according to our data. Variant chr6-83853428-G-A is described in ClinVar as [Benign]. Clinvar id is 1165051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.86 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIPPLY2	NM_001009994.3 linkuse as main transcript	c.12G>A	p.Ala4Ala	synonymous_variant	1/4	ENST00000369689.6	NP_001009994.1	Q5TAB7-1
RIPPLY2	NM_001400900.1 linkuse as main transcript	c.12G>A	p.Ala4Ala	synonymous_variant	1/3		NP_001387829.1
RIPPLY2-CYB5R4	NR_174604.1 linkuse as main transcript	n.69G>A		non_coding_transcript_exon_variant	1/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIPPLY2	ENST00000369689.6 linkuse as main transcript	c.12G>A	p.Ala4Ala	synonymous_variant	1/4	1	NM_001009994.3	ENSP00000358703.1		Q5TAB7-1
ENSG00000287705	ENST00000656981.1 linkuse as main transcript	n.740C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.244

AC:

37054

AN:

152098

Hom.:

8005

Cov.:

show subpopulations

Gnomad AFR

AF:

0.569

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.277

Gnomad ASJ

AF:

0.0784

Gnomad EAS

AF:

0.268

Gnomad SAS

AF:

0.0689

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.0809

Gnomad OTH

AF:

0.193

GnomAD3 exomes

AF:

0.168

AC:

22998

AN:

136808

Hom.:

3553

AF XY:

0.150

AC XY:

11138

AN XY:

74336

show subpopulations

Gnomad AFR exome

AF:

0.596

Gnomad AMR exome

AF:

0.353

Gnomad ASJ exome

AF:

0.0833

Gnomad EAS exome

AF:

0.272

Gnomad SAS exome

AF:

0.0672

Gnomad FIN exome

AF:

0.112

Gnomad NFE exome

AF:

0.0780

Gnomad OTH exome

AF:

0.126

GnomAD4 exome

AF:

0.102

AC:

142325

AN:

1390588

Hom.:

13456

Cov.:

AF XY:

0.0992

AC XY:

68029

AN XY:

686082

show subpopulations

Gnomad4 AFR exome

AF:

0.589

Gnomad4 AMR exome

AF:

0.337

Gnomad4 ASJ exome

AF:

0.0777

Gnomad4 EAS exome

AF:

0.239

Gnomad4 SAS exome

AF:

0.0662

Gnomad4 FIN exome

AF:

0.113

Gnomad4 NFE exome

AF:

0.0773

Gnomad4 OTH exome

AF:

0.129

GnomAD4 genome

AF:

0.244

AC:

37163

AN:

152216

Hom.:

8046

Cov.:

AF XY:

0.243

AC XY:

18085

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.570

Gnomad4 AMR

AF:

0.277

Gnomad4 ASJ

AF:

0.0784

Gnomad4 EAS

AF:

0.267

Gnomad4 SAS

AF:

0.0689

Gnomad4 FIN

AF:

0.114

Gnomad4 NFE

AF:

0.0809

Gnomad4 OTH

AF:

0.197

Alfa

AF:

0.124

Hom.:

805

Bravo

AF:

0.275

Asia WGS

AF:

0.179

AC:

623

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Spondylocostal dysostosis 6, autosomal recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

3.4

DANN

Benign

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over