Genetic Variant SHOC2:c.-243C>T (chr10-110919433-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001324336.2(SHOC2):c.-243C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0669 in 393,454 control chromosomes in the GnomAD database, including 2,189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.071 ( 763 hom., cov: 28)

Exomes 𝑓: 0.064 ( 1426 hom. )

Consequence

SHOC2
NM_001324336.2 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.15

Variant links:

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]

SHOC2 links:

BBIP1 (HGNC:28093): (BBSome interacting protein 1) This gene encodes one of eight proteins that form the BBSome complex and is essential for its assembly. The BBSome complex is involved in trafficking signal receptors to and from the cilia. Mutations in this gene result in Bardet-Biedl syndrome 18. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

BBIP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 10-110919433-C-T is Benign according to our data. Variant chr10-110919433-C-T is described in ClinVar as [Benign]. Clinvar id is 1302751.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SHOC2	NM_007373.4 link	c.-459C>T		upstream_gene_variant		ENST00000369452.9	NP_031399.2	Q9UQ13-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SHOC2	ENST00000369452.9 link	c.-459C>T		upstream_gene_variant		1	NM_007373.4	ENSP00000358464.5		Q9UQ13-1

Frequencies

GnomAD3 genomes

AF:

0.0711

AC:

10756

AN:

151194

Hom.:

751

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0809

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.0360

Gnomad EAS

AF:

0.299

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.0372

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0270

Gnomad OTH

AF:

0.0689

GnomAD4 exome

AF:

0.0642

AC:

15537

AN:

242144

Hom.:

1426

Cov.:

AF XY:

0.0618

AC XY:

7596

AN XY:

122844

show subpopulations

Gnomad4 AFR exome

AF:

0.0816

Gnomad4 AMR exome

AF:

0.218

Gnomad4 ASJ exome

AF:

0.0346

Gnomad4 EAS exome

AF:

0.288

Gnomad4 SAS exome

AF:

0.148

Gnomad4 FIN exome

AF:

0.0324

Gnomad4 NFE exome

AF:

0.0274

Gnomad4 OTH exome

AF:

0.0737

GnomAD4 genome

AF:

0.0713

AC:

10791

AN:

151310

Hom.:

763

Cov.:

AF XY:

0.0774

AC XY:

5723

AN XY:

73904

show subpopulations

Gnomad4 AFR

AF:

0.0810

Gnomad4 AMR

AF:

0.180

Gnomad4 ASJ

AF:

0.0360

Gnomad4 EAS

AF:

0.299

Gnomad4 SAS

AF:

0.146

Gnomad4 FIN

AF:

0.0372

Gnomad4 NFE

AF:

0.0270

Gnomad4 OTH

AF:

0.0687

Alfa

AF:

0.0261

Hom.:

Bravo

AF:

0.0803

Asia WGS

AF:

0.194

AC:

674

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.97

DANN

Benign

0.73

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over