2-219550995-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015311.3(OBSL1):c.5684-153C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 1,496,186 control chromosomes in the GnomAD database, including 217,317 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.48 (18637 hom., cov: 32)
  • Exomes 𝑓: 0.54 (198680 hom.)
• Consequence: OBSL1 NM_015311.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.704

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 2-219550995-G-A is Benign according to our data. Variant chr2-219550995-G-A is described in ClinVar as [Benign]. Clinvar id is 1296814.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OBSL1	NM_015311.3	c.5684-153C>T		intron_variant		ENST00000404537.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OBSL1	ENST00000404537.6	c.5684-153C>T		intron_variant		1	NM_015311.3	P1

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73332 AN: 151802 Hom.: 18631 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.530

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.533

GnomAD4 exome AF: 0.539 AC: 724595 AN: 1344266 Hom.: 198680 Cov.: 49 AF XY: 0.546 AC XY: 359507 AN XY: 658624

Gnomad4 AFR exome AF: 0.340

Gnomad4 AMR exome AF: 0.441

Gnomad4 ASJ exome AF: 0.665

Gnomad4 EAS exome AF: 0.645

Gnomad4 SAS exome AF: 0.738

Gnomad4 FIN exome AF: 0.494

Gnomad4 NFE exome AF: 0.528

Gnomad4 OTH exome AF: 0.548

GnomAD4 genome AF: 0.483 AC: 73360 AN: 151920 Hom.: 18637 Cov.: 32 AF XY: 0.484 AC XY: 35887 AN XY: 74218

Gnomad4 AFR AF: 0.344

Gnomad4 AMR AF: 0.472

Gnomad4 ASJ AF: 0.647

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.533

Gnomad4 OTH AF: 0.538

Alfa AF: 0.539 Hom.: 10272

Bravo AF: 0.474

Asia WGS AF: 0.664 AC: 2302 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	7.9
Dann	Benign	0.80

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: rs3731918; hg19: chr2-220415717; COSMIC: COSV54705738; COSMIC: COSV54705738;