rs72819758
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2
The NM_007373.4(SHOC2):c.-159T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00383 in 1,138,158 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0030 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0040 ( 11 hom. )
Consequence
SHOC2
NM_007373.4 5_prime_UTR
NM_007373.4 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.95
Genes affected
SHOC2 (HGNC:15454): (SHOC2 leucine rich repeat scaffold protein) This gene encodes a protein that consists almost entirely of leucine-rich repeats, a domain implicated in protein-protein interactions. The protein may function as a scaffold linking RAS to downstream signal transducers in the RAS/ERK MAP kinase signaling cascade. Mutations in this gene have been associated with Noonan-like syndrome with loose anagen hair. [provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
Variant 10-110964200-T-C is Benign according to our data. Variant chr10-110964200-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 40632.We mark this variant Likely_benign, oryginal submissions are: {Benign=3, Uncertain_significance=1}.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00301 (458/152254) while in subpopulation AMR AF= 0.00582 (89/15280). AF 95% confidence interval is 0.00485. There are 2 homozygotes in gnomad4. There are 219 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 458 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SHOC2 | NM_007373.4 | c.-159T>C | 5_prime_UTR_variant | 2/9 | ENST00000369452.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SHOC2 | ENST00000369452.9 | c.-159T>C | 5_prime_UTR_variant | 2/9 | 1 | NM_007373.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00300 AC: 457AN: 152136Hom.: 2 Cov.: 32
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GnomAD4 exome AF: 0.00396 AC: 3900AN: 985904Hom.: 11 Cov.: 13 AF XY: 0.00378 AC XY: 1872AN XY: 495686
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GnomAD4 genome ? AF: 0.00301 AC: 458AN: 152254Hom.: 2 Cov.: 32 AF XY: 0.00294 AC XY: 219AN XY: 74458
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Noonan syndrome and Noonan-related syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jan 05, 2017 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 07, 2011 | -159T>C (no amino acid change) in SHOC2 exon 2: The -159T>C variant has not been previously reported in the literature but has been identified in our laboratory in four other probands. This variant is located in the 5'UTR and variants in re gulatory regions could have an effect on transcriptional or translational effici ency. However, only a single recurrent variant in SHOC2 has been proven to be pa thogenic to date. - |
Noonan syndrome-like disorder with loose anagen hair 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at