2-219564524-C-G

Position:

• chr2-219564524-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015311.3(OBSL1):​c.2407+718G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 152,192 control chromosomes in the GnomAD database, including 25,813 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 0.56 (25813 hom., cov: 34)
• Consequence: OBSL1 NM_015311.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0320

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OBSL1	NM_015311.3	c.2407+718G>C		intron_variant		ENST00000404537.6	NP_056126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OBSL1	ENST00000404537.6	c.2407+718G>C		intron_variant		1	NM_015311.3	ENSP00000385636	P1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84969 AN: 152074 Hom.: 25794 Cov.: 34

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.596

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.559 AC: 85023 AN: 152192 Hom.: 25813 Cov.: 34 AF XY: 0.563 AC XY: 41904 AN XY: 74408

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.672

Gnomad4 SAS AF: 0.729

Gnomad4 FIN AF: 0.706

Gnomad4 NFE AF: 0.669

Gnomad4 OTH AF: 0.599

Alfa AF: 0.615 Hom.: 3777

Bravo AF: 0.531

Asia WGS AF: 0.686 AC: 2387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.6
DANN	Benign	0.73

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: rs907141; hg19: chr2-220429246;