rs188765124

Variant names:

• chr10-110964234-C-T
• rs188765124
• NM_007373.4:c.-125C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_007373.4(SHOC2):​c.-125C>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 0.0000454 in 1,431,582 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 (★). The gene SHOC2 is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000047 (0 hom.)
• Consequence: SHOC2 NM_007373.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.109
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• Noonan syndrome-like disorder with loose anagen hair

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Noonan syndrome-like disorder with loose anagen hair 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P, PanelApp Australia
• cardiofaciocutaneous syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• Costello syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• Noonan syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• Noonan syndrome with multiple lentigines

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Specifications for SHOC2 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-110964234-C-T is Benign according to our data. Variant chr10-110964234-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 165237.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007373.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHOC2	NM_007373.4	MANE Select	c.-125C>T		5_prime_UTR	Exon 2 of 9	NP_031399.2
	SHOC2	NM_001324336.2		c.-125C>T		5_prime_UTR	Exon 2 of 9	NP_001311265.1	Q9UQ13-1
	SHOC2	NM_001324337.2		c.-125C>T		5_prime_UTR	Exon 3 of 10	NP_001311266.1	Q9UQ13-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHOC2	ENST00000369452.9	TSL:1 MANE Select	c.-125C>T		5_prime_UTR	Exon 2 of 9	ENSP00000358464.5	Q9UQ13-1
	SHOC2	ENST00000685059.1		c.-125C>T		5_prime_UTR	Exon 3 of 10	ENSP00000510210.1	Q9UQ13-1
	SHOC2	ENST00000688928.1		c.-125C>T		5_prime_UTR	Exon 2 of 9	ENSP00000509273.1	Q9UQ13-1

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152122 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000469 AC: 60 AN: 1279342 Hom.: 0 Cov.: 19 AF XY: 0.0000567 AC XY: 36 AN XY: 634520

African (AFR) AF: 0.00 AC: 0 AN: 27796

American (AMR) AF: 0.00 AC: 0 AN: 25608

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22324

East Asian (EAS) AF: 0.00 AC: 0 AN: 35236

South Asian (SAS) AF: 0.00 AC: 0 AN: 70632

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41726

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3852

European-Non Finnish (NFE) AF: 0.0000551 AC: 55 AN: 998730

Other (OTH) AF: 0.0000936 AC: 5 AN: 53438

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152240 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74442

African (AFR) AF: 0.00 AC: 0 AN: 41558

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.7
DANN	Benign	0.74
PhyloP100		-0.11

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

Other links and lift over

dbSNP: rs188765124; hg19: chr10-112723992;