chr2-219559765-G-C

Variant names:

• chr2-219559765-G-C
• rs1039900
• NM_015311.3:c.2954-268C>G

Variant summary

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

The NM_015311.3(OBSL1):​c.2954-268C>G variant causes a intron 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: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OBSL1 NM_015311.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0540
• Publications: 6 publications found

Genes affected

OBSL1 (HGNC:29092): (obscurin like cytoskeletal adaptor 1) Cytoskeletal adaptor proteins function in linking the internal cytoskeleton of cells to the cell membrane. This gene encodes a cytoskeletal adaptor protein, which is a member of the Unc-89/obscurin family. The protein contains multiple N- and C-terminal immunoglobulin (Ig)-like domains and a central fibronectin type 3 domain. Mutations in this gene cause 3M syndrome type 2. Alternatively spliced transcript variants encoding different isoforms have been found in this gene. [provided by RefSeq, Mar 2010]

OBSL1 Gene-Disease associations (from GenCC):

• 3M syndrome 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• 3-M syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000269068 (HGNC:):

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=-0.83).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015311.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OBSL1	NM_015311.3	MANE Select	c.2954-268C>G		intron	N/A	NP_056126.1
	OBSL1	NM_001173431.2		c.2954-268C>G		intron	N/A	NP_001166902.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OBSL1	ENST00000404537.6	TSL:1 MANE Select	c.2954-268C>G		intron	N/A	ENSP00000385636.1
	OBSL1	ENST00000953546.1		c.2966-268C>G		intron	N/A	ENSP00000623605.1
	OBSL1	ENST00000953548.1		c.2897-268C>G		intron	N/A	ENSP00000623607.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 310912 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 159962

African (AFR) AF: 0.00 AC: 0 AN: 10490

American (AMR) AF: 0.00 AC: 0 AN: 12562

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10592

East Asian (EAS) AF: 0.00 AC: 0 AN: 24692

South Asian (SAS) AF: 0.00 AC: 0 AN: 21358

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 19590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1472

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 190998

Other (OTH) AF: 0.00 AC: 0 AN: 19158

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 2505

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.32
PhyloP100		0.054
PromoterAI		-0.0064	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1039900; hg19: chr2-220424487;