rs492899

chr6-31965741-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006929.5(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 NM_006929.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.30

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt
SKIC2	NM_006929.5	c.1972-42T>C		intron_variant		ENST00000375394.7
SKIC2	XM_011514815.4	c.1972-42T>C		intron_variant
SKIC2	XM_047419259.1	c.1972-42T>C		intron_variant
SKIC2	XM_047419260.1	c.1972-42T>C		intron_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22847 AN: 152086 Hom.: 2224 Cov.: 33

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

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.: 15 AF XY: 0.106 AC XY: 59481 AN XY: 558796

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.: 33 AF XY: 0.154 AC XY: 11463 AN XY: 74432

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

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

Other links and lift over

dbSNP: rs492899; hg19: chr6-31933518;