Variant rs492899 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000375394.7(SKIC2):c.1972-42T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,252,492 control chromosomes in the GnomAD database, including 9,645 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2235 hom., cov: 33)

Exomes 𝑓: 0.10 ( 7410 hom. )

Consequence

SKIC2
ENST00000375394.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.30

Variant links:

Genes affected

SKIC2 (HGNC:10898): (SKI2 subunit of superkiller complex) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which is a human homologue of yeast SKI2 and may be involved in antiviral activity by blocking translation of poly(A) deficient mRNAs. This gene is located in the class III region of the major histocompatibility complex. [provided by RefSeq, Jul 2008]

SKIC2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 6-31965741-T-C is Benign according to our data. Variant chr6-31965741-T-C is described in ClinVar as [Benign]. Clinvar id is 1228348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
SKIC2	NM_006929.5 linkuse as main transcript	c.1972-42T>C	intron_variant	ENST00000375394.7	NP_008860.4
SKIC2	XM_011514815.4 linkuse as main transcript	c.1972-42T>C	intron_variant		XP_011513117.1
SKIC2	XM_047419259.1 linkuse as main transcript	c.1972-42T>C	intron_variant		XP_047275215.1
SKIC2	XM_047419260.1 linkuse as main transcript	c.1972-42T>C	intron_variant		XP_047275216.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SKIC2	ENST00000375394.7 linkuse as main transcript	c.1972-42T>C		intron_variant		1	NM_006929.5	ENSP00000364543	P1

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22847

AN:

152086

Hom.:

2224

Cov.:

show subpopulations

Gnomad AFR

AF:

0.269

Gnomad AMI

AF:

0.145

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.0770

Gnomad EAS

AF:

0.0991

Gnomad SAS

AF:

0.186

Gnomad FIN

AF:

0.163

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.0873

Gnomad OTH

AF:

0.166

GnomAD3 exomes

AF:

0.119

AC:

27925

AN:

235250

Hom.:

2211

AF XY:

0.123

AC XY:

15763

AN XY:

127728

show subpopulations

Gnomad AFR exome

AF:

0.273

Gnomad AMR exome

AF:

0.0791

Gnomad ASJ exome

AF:

0.0799

Gnomad EAS exome

AF:

0.103

Gnomad SAS exome

AF:

0.206

Gnomad FIN exome

AF:

0.152

Gnomad NFE exome

AF:

0.0858

Gnomad OTH exome

AF:

0.116

GnomAD4 exome

AF:

0.102

AC:

112265

AN:

1100288

Hom.:

7410

Cov.:

AF XY:

0.106

AC XY:

59481

AN XY:

558796

show subpopulations

Gnomad4 AFR exome

AF:

0.272

Gnomad4 AMR exome

AF:

0.0855

Gnomad4 ASJ exome

AF:

0.0835

Gnomad4 EAS exome

AF:

0.0826

Gnomad4 SAS exome

AF:

0.209

Gnomad4 FIN exome

AF:

0.149

Gnomad4 NFE exome

AF:

0.0835

Gnomad4 OTH exome

AF:

0.111

GnomAD4 genome

AF:

0.150

AC:

22899

AN:

152204

Hom.:

2235

Cov.:

AF XY:

0.154

AC XY:

11463

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.269

Gnomad4 AMR

AF:

0.119

Gnomad4 ASJ

AF:

0.0770

Gnomad4 EAS

AF:

0.0993

Gnomad4 SAS

AF:

0.188

Gnomad4 FIN

AF:

0.163

Gnomad4 NFE

AF:

0.0873

Gnomad4 OTH

AF:

0.169

Alfa

AF:

0.0983

Hom.:

1653

Bravo

AF:

0.149

Asia WGS

AF:

0.187

AC:

649

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Trichohepatoenteric syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.030

DANN

Benign

0.52

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

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