10-110937483-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007373.4(SHOC2):c.-235+17826C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 152,106 control chromosomes in the GnomAD database, including 44,074 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.76 (44074 hom., cov: 31)
• Consequence: SHOC2 NM_007373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.652

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHOC2	NM_007373.4	c.-235+17826C>T		intron_variant		ENST00000369452.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHOC2	ENST00000369452.9	c.-235+17826C>T		intron_variant		1	NM_007373.4	P1

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115376 AN: 151988 Hom.: 44059 Cov.: 31

Gnomad AFR AF: 0.688

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.806

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.771

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.759 AC: 115435 AN: 152106 Hom.: 44074 Cov.: 31 AF XY: 0.761 AC XY: 56626 AN XY: 74390

Gnomad4 AFR AF: 0.688

Gnomad4 AMR AF: 0.847

Gnomad4 ASJ AF: 0.770

Gnomad4 EAS AF: 0.848

Gnomad4 SAS AF: 0.806

Gnomad4 FIN AF: 0.766

Gnomad4 NFE AF: 0.771

Gnomad4 OTH AF: 0.749

Alfa AF: 0.773 Hom.: 92059

Bravo AF: 0.760

Asia WGS AF: 0.775 AC: 2698 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	7.5
Dann	Benign	0.25

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: rs10787292; hg19: chr10-112697241;