10-110919872-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007373.4(SHOC2):c.-235+215G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 359,896 control chromosomes in the GnomAD database, including 2,815 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.098 (977 hom., cov: 29)
  • Exomes 𝑓: 0.12 (1838 hom.)
• Consequence: SHOC2 NM_007373.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.927

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-110919872-G-C is Benign according to our data. Variant chr10-110919872-G-C is described in ClinVar as [Benign]. Clinvar id is 1291539.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHOC2	NM_007373.4	c.-235+215G>C		intron_variant		ENST00000369452.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHOC2	ENST00000369452.9	c.-235+215G>C		intron_variant		1	NM_007373.4	P1

Frequencies

GnomAD3 genomes AF: 0.0981 AC: 14784 AN: 150678 Hom.: 976 Cov.: 29

Gnomad AFR AF: 0.0259

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.0962

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0366

Gnomad SAS AF: 0.0414

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.112

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.115

GnomAD4 exome AF: 0.125 AC: 26087 AN: 209104 Hom.: 1838 AF XY: 0.126 AC XY: 13454 AN XY: 106776

Gnomad4 AFR exome AF: 0.0256

Gnomad4 AMR exome AF: 0.0840

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.0281

Gnomad4 SAS exome AF: 0.0364

Gnomad4 FIN exome AF: 0.142

Gnomad4 NFE exome AF: 0.144

Gnomad4 OTH exome AF: 0.119

GnomAD4 genome AF: 0.0981 AC: 14786 AN: 150792 Hom.: 977 Cov.: 29 AF XY: 0.0973 AC XY: 7165 AN XY: 73668

Gnomad4 AFR AF: 0.0258

Gnomad4 AMR AF: 0.0959

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.0367

Gnomad4 SAS AF: 0.0422

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.115

Alfa AF: 0.122 Hom.: 174

Bravo AF: 0.0926

Asia WGS AF: 0.0400 AC: 137 AN: 3412

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	13
Dann	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.4

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: rs149246154; hg19: chr10-112679630;