2-219559471-G-C

Variant names:

• chr2-219559471-G-C
• NM_015311.3:c.2980C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015311.3(OBSL1):​c.2980C>G​(p.Arg994Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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)
• Consequence: OBSL1 NM_015311.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.87

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]

ENSG00000269068 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40395105).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OBSL1	NM_015311.3	c.2980C>G	p.Arg994Gly	missense_variant	Exon 9 of 21	ENST00000404537.6	NP_056126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OBSL1	ENST00000404537.6	c.2980C>G	p.Arg994Gly	missense_variant	Exon 9 of 21	1	NM_015311.3	ENSP00000385636.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T;.;.
Eigen	Benign	-0.013
Eigen_PC	Benign	0.020
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.14	N;.;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-2.2	N;N;.
REVEL	Benign	0.17
Sift	Benign	0.054	T;T;.
Sift4G	Benign	0.066	T;D;T
Polyphen		0.30	B;.;.
Vest4		0.47
MutPred		0.55		Loss of stability (P = 0.0631);Loss of stability (P = 0.0631);Loss of stability (P = 0.0631);
MVP		0.62
MPC		0.27
ClinPred		0.60	D
GERP RS		4.3
Varity_R		0.12
gMVP		0.53

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-220424193;