2-219550873-GGA-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_015311.3(OBSL1):c.5684-33_5684-32del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,604,324 control chromosomes in the GnomAD database, including 162,392 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (14817 hom., cov: 0)
  • Exomes 𝑓: 0.45 (147575 hom.)
• Consequence: OBSL1 NM_015311.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.22

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 -16 ACMG points.

• BP6: Variant 2-219550873-GGA-G is Benign according to our data. Variant chr2-219550873-GGA-G is described in ClinVar as [Benign]. Clinvar id is 1276422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OBSL1	NM_015311.3	c.5684-33_5684-32del		intron_variant		ENST00000404537.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OBSL1	ENST00000404537.6	c.5684-33_5684-32del		intron_variant		1	NM_015311.3	P1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66406 AN: 151702 Hom.: 14809 Cov.: 0

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.519

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.410

GnomAD3 exomes AF: 0.426 AC: 98830 AN: 232190 Hom.: 21760 AF XY: 0.414 AC XY: 52183 AN XY: 125954

Gnomad AFR exome AF: 0.385

Gnomad AMR exome AF: 0.534

Gnomad ASJ exome AF: 0.320

Gnomad EAS exome AF: 0.407

Gnomad SAS exome AF: 0.244

Gnomad FIN exome AF: 0.513

Gnomad NFE exome AF: 0.445

Gnomad OTH exome AF: 0.406

GnomAD4 exome AF: 0.446 AC: 647892 AN: 1452504 Hom.: 147575 AF XY: 0.439 AC XY: 317184 AN XY: 721750

Gnomad4 AFR exome AF: 0.389

Gnomad4 AMR exome AF: 0.528

Gnomad4 ASJ exome AF: 0.329

Gnomad4 EAS exome AF: 0.356

Gnomad4 SAS exome AF: 0.257

Gnomad4 FIN exome AF: 0.507

Gnomad4 NFE exome AF: 0.464

Gnomad4 OTH exome AF: 0.424

GnomAD4 genome AF: 0.438 AC: 66449 AN: 151820 Hom.: 14817 Cov.: 0 AF XY: 0.439 AC XY: 32535 AN XY: 74176

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.519

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.406

Alfa AF: 0.435 Hom.: 2687

Bravo AF: 0.437

Asia WGS AF: 0.312 AC: 1092 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

3M syndrome 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs146790993; hg19: chr2-220415595;