rs750568201
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_007373.4(SHOC2):āc.303T>Cā(p.Asn101=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.000012 ( 0 hom. )
Consequence
SHOC2
NM_007373.4 synonymous
NM_007373.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.882
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
Variant 10-110964661-T-C is Benign according to our data. Variant chr10-110964661-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 260162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.882 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0000123 (18/1461834) while in subpopulation AMR AF= 0.000403 (18/44718). AF 95% confidence interval is 0.000259. There are 0 homozygotes in gnomad4_exome. There are 11 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAdExome4 at 18 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SHOC2 | NM_007373.4 | c.303T>C | p.Asn101= | synonymous_variant | 2/9 | ENST00000369452.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SHOC2 | ENST00000369452.9 | c.303T>C | p.Asn101= | synonymous_variant | 2/9 | 1 | NM_007373.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152098Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000637 AC: 16AN: 250996Hom.: 0 AF XY: 0.0000737 AC XY: 10AN XY: 135640
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GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461834Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11AN XY: 727218
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152098Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74292
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Mar 28, 2018 | The c.303T>C p.Asn101Asn variant (rs750568201, ClinVar variant ID 260162), to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the genome Aggregation Database (gnomAD) with a Latino population frequency of 0.04% (identified on 14 out of 33,560 chromosomes). The variant affects a weakly conserved nucleotide, and computational splice site prediction algorithms do not predict a change in the nearest splice site or creation of a cryptic splice site. Based on the available information, the c.303T>C variant is likely to be benign. - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 23, 2019 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
RASopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 07, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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