NM_001324336.2:c.-243C>A

Variant names:

• chr10-110919433-C-A
• rs3750622
• NM_001324336.2:c.-243C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001324336.2(SHOC2):​c.-243C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 28)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SHOC2 NM_001324336.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).

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.-243C>A		5_prime_UTR	Exon 1 of 9	NP_001311265.1	Q9UQ13-1
	SHOC2	NM_007373.4	MANE Select	c.-459C>A		upstream_gene	N/A	NP_031399.2
	SHOC2	NM_001324337.2		c.-644C>A		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.-243C>A		5_prime_UTR	Exon 1 of 9	ENSP00000509273.1	Q9UQ13-1
	SHOC2	ENST00000902509.1		c.-235+1368C>A		intron	N/A	ENSP00000572568.1
	SHOC2	ENST00000902510.1		c.-235+436C>A		intron	N/A	ENSP00000572569.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 242202 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 122878

African (AFR) AF: 0.00 AC: 0 AN: 7020

American (AMR) AF: 0.00 AC: 0 AN: 7298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9106

East Asian (EAS) AF: 0.00 AC: 0 AN: 22740

South Asian (SAS) AF: 0.00 AC: 0 AN: 2190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1278

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 155862

Other (OTH) AF: 0.00 AC: 0 AN: 16134

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.66
DANN	Benign	0.63
PhyloP100		-2.2
PromoterAI		0.0020	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3750622; hg19: chr10-112679191;