Variant rs1555939381 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_006941.4(SOX10):c.219_428+43del variant causes a splice donor, splice donor 5th base, coding sequence, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

SOX10
NM_006941.4 splice_donor, splice_donor_5th_base, coding_sequence, intron

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.68

Variant links:

Genes affected

SOX10 (HGNC:11190): (SRY-box transcription factor 10) This gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. The encoded protein may act as a transcriptional activator after forming a protein complex with other proteins. This protein acts as a nucleocytoplasmic shuttle protein and is important for neural crest and peripheral nervous system development. Mutations in this gene are associated with Waardenburg-Shah and Waardenburg-Hirschsprung disease. [provided by RefSeq, Jul 2008]

SOX10 links:

POLR2F (HGNC:9193): (RNA polymerase II, I and III subunit F) This gene encodes the sixth largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. In yeast, this polymerase subunit, in combination with at least two other subunits, forms a structure that stabilizes the transcribing polymerase on the DNA template. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

POLR2F links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 22-37983313-CCGAAGCTAGAGGGCCCGAGCCCGGGGGGCGGTCGGGTGCTCACCTCCAGAGCTTGCCCAGCGTCTTGCTGAGCTCAGCGTTGTGCAGGTGCGGGTACTGGTCCGCGAGCTTCCTGCGCGCTGCCTGAGCCCACACCATGAAGGCGTTCATGGGCCGCTTGACGTGCGGCTTGCTTTTGCTGGCGCCGTTGACGCGCACGGGCATGGGCACCAGCGTCCAGTCGTAGCCGCTGAGCACCTGGCTGACGGCCTCG-C is Pathogenic according to our data. Variant chr22-37983313-CCGAAGCTAGAGGGCCCGAGCCCGGGGGGCGGTCGGGTGCTCACCTCCAGAGCTTGCCCAGCGTCTTGCTGAGCTCAGCGTTGTGCAGGTGCGGGTACTGGTCCGCGAGCTTCCTGCGCGCTGCCTGAGCCCACACCATGAAGGCGTTCATGGGCCGCTTGACGTGCGGCTTGCTTTTGCTGGCGCCGTTGACGCGCACGGGCATGGGCACCAGCGTCCAGTCGTAGCCGCTGAGCACCTGGCTGACGGCCTCG-C is described in ClinVar as [Pathogenic]. Clinvar id is 7405.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr22-37983313-CCGAAGCTAGAGGGCCCGAGCCCGGGGGGCGGTCGGGTGCTCACCTCCAGAGCTTGCCCAGCGTCTTGCTGAGCTCAGCGTTGTGCAGGTGCGGGTACTGGTCCGCGAGCTTCCTGCGCGCTGCCTGAGCCCACACCATGAAGGCGTTCATGGGCCGCTTGACGTGCGGCTTGCTTTTGCTGGCGCCGTTGACGCGCACGGGCATGGGCACCAGCGTCCAGTCGTAGCCGCTGAGCACCTGGCTGACGGCCTCG-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
SOX10	NM_006941.4 linkuse as main transcript	c.219_428+43del	splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	2/4	ENST00000396884.8
POLR2F	NM_001301130.2 linkuse as main transcript	c.294-2838_294-2586del	intron_variant
POLR2F	NM_001301131.2 linkuse as main transcript	c.293+16146_293+16398del	intron_variant
POLR2F	NM_001363825.1 linkuse as main transcript	c.38+11006_38+11258del	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX10	ENST00000396884.8 linkuse as main transcript	c.219_428+43del		splice_donor_variant, splice_donor_5th_base_variant, coding_sequence_variant, intron_variant	2/4	1	NM_006941.4	P1	P56693-1

Frequencies

GnomAD3 genomes

Cov.:

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

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Waardenburg syndrome type 2E, without neurologic involvement

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Dec 01, 2007

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.