rs1203298501

Variant names:

• chr10-110919546-T-C
• rs1203298501
• NM_001324336.2:c.-235+105T>C

Your query was ambiguous. Multiple possible variants found:

• chr10-110919546-T-C
• chr10-110919546-T-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001324336.2(SHOC2):​c.-235+105T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.00012 (0 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: SHOC2 NM_001324336.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.260
• 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]

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 Gene-Disease associations (from GenCC):

• Bardet-Biedl syndrome 18

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• Bardet-Biedl syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001324336.2. 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_001324336.2		c.-235+105T>C		intron	N/A	NP_001311265.1	Q9UQ13-1
	SHOC2	NM_007373.4	MANE Select	c.-346T>C		upstream_gene	N/A	NP_031399.2
	SHOC2	NM_001324337.2		c.-531T>C		upstream_gene	N/A	NP_001311266.1	Q9UQ13-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SHOC2	ENST00000688928.1		c.-235+105T>C		intron	N/A	ENSP00000509273.1	Q9UQ13-1
	SHOC2	ENST00000902509.1		c.-235+1481T>C		intron	N/A	ENSP00000572568.1
	SHOC2	ENST00000902510.1		c.-235+549T>C		intron	N/A	ENSP00000572569.1

Frequencies

GnomAD3 genomes AF: 0.0000625 AC: 1 AN: 15988 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000244

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000125 AC: 2 AN: 16026 Hom.: 0 Cov.: 0 AF XY: 0.000139 AC XY: 1 AN XY: 7204

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000243 AC: 1 AN: 4118

American (AMR) AF: 0.000602 AC: 1 AN: 1662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 430

East Asian (EAS) AF: 0.00 AC: 0 AN: 280

South Asian (SAS) AF: 0.00 AC: 0 AN: 396

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1120

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 26

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 7748

Other (OTH) AF: 0.00 AC: 0 AN: 214

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	13
DANN	Benign	0.72
PhyloP100		-0.26
PromoterAI		-0.012	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1203298501; hg19: chr10-112679304;