10-110944622-T-C

Position:

• chr10-110944622-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SHOC2	NM_007373.4	c.-234-19503T>C		intron_variant		ENST00000369452.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SHOC2	ENST00000369452.9	c.-234-19503T>C		intron_variant		1	NM_007373.4	P1

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

Gnomad4 AFR AF: 0.683

Gnomad4 AMR AF: 0.837

Gnomad4 ASJ AF: 0.746

Gnomad4 EAS AF: 0.844

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.757

Gnomad4 NFE AF: 0.747

Gnomad4 OTH AF: 0.730

Alfa AF: 0.702 Hom.: 2998

Bravo AF: 0.745

Asia WGS AF: 0.732 AC: 2544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.7
DANN	Benign	0.60

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: rs1359849; hg19: chr10-112704380;