NM_007373.4:c.-234-19503T>C

Variant names:

• chr10-110944622-T-C
• rs1359849
• NM_007373.4:c.-234-19503T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007373.4(SHOC2):​c.-234-19503T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,130 control chromosomes in the GnomAD database, including 41,980 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 0.74 (41980 hom., cov: 33)
• Consequence: SHOC2 NM_007373.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300
• 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: ClinGen, Orphanet
• Noonan syndrome-like disorder with loose anagen hair 1

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

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.-234-19503T>C		intron	N/A	NP_031399.2
	SHOC2	NM_001324336.2		c.-234-19503T>C		intron	N/A	NP_001311265.1
	SHOC2	NM_001324337.2		c.-419-6986T>C		intron	N/A	NP_001311266.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHOC2	ENST00000369452.9	TSL:1 MANE Select	c.-234-19503T>C		intron	N/A	ENSP00000358464.5
	SHOC2	ENST00000685059.1		c.-285-10794T>C		intron	N/A	ENSP00000510210.1
	SHOC2	ENST00000688928.1		c.-234-19503T>C		intron	N/A	ENSP00000509273.1

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112599 AN: 152012 Hom.: 41965 Cov.: 33

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.746

Gnomad EAS AF: 0.843

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.720

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.739

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

GnomAD4 genome AF: 0.741 AC: 112660 AN: 152130 Hom.: 41980 Cov.: 33 AF XY: 0.742 AC XY: 55201 AN XY: 74370

African (AFR) AF: 0.683 AC: 28320 AN: 41456

American (AMR) AF: 0.837 AC: 12799 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.746 AC: 2589 AN: 3472

East Asian (EAS) AF: 0.844 AC: 4380 AN: 5192

South Asian (SAS) AF: 0.702 AC: 3389 AN: 4828

European-Finnish (FIN) AF: 0.757 AC: 8008 AN: 10582

Middle Eastern (MID) AF: 0.719 AC: 210 AN: 292

European-Non Finnish (NFE) AF: 0.747 AC: 50786 AN: 67998

Other (OTH) AF: 0.730 AC: 1543 AN: 2114

Alfa AF: 0.703 Hom.: 3199

Bravo AF: 0.745

Asia WGS AF: 0.732 AC: 2544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.7
DANN	Benign	0.60
PhyloP100		0.0030
Mutation Taster		=100/0	polymorphism (auto)

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: rs1359849; hg19: chr10-112704380;