2-219550924-T-C

Position:

• chr2-219550924-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015311.3(OBSL1):​c.5684-82A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 1,567,400 control chromosomes in the GnomAD database, including 159,017 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (14883 hom., cov: 32)
  • Exomes 𝑓: 0.45 (144134 hom.)
• Consequence: OBSL1 NM_015311.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.258

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-219550924-T-C is Benign according to our data. Variant chr2-219550924-T-C is described in ClinVar as [Benign]. Clinvar id is 1287989.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OBSL1	NM_015311.3	c.5684-82A>G		intron_variant		ENST00000404537.6	NP_056126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OBSL1	ENST00000404537.6	c.5684-82A>G		intron_variant		1	NM_015311.3	ENSP00000385636	P1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66531 AN: 151722 Hom.: 14874 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.420

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.362

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.410

GnomAD4 exome AF: 0.447 AC: 632284 AN: 1415560 Hom.: 144134 Cov.: 42 AF XY: 0.440 AC XY: 308303 AN XY: 700228

Gnomad4 AFR exome AF: 0.388

Gnomad4 AMR exome AF: 0.530

Gnomad4 ASJ exome AF: 0.330

Gnomad4 EAS exome AF: 0.352

Gnomad4 SAS exome AF: 0.259

Gnomad4 FIN exome AF: 0.510

Gnomad4 NFE exome AF: 0.464

Gnomad4 OTH exome AF: 0.424

GnomAD4 genome AF: 0.438 AC: 66575 AN: 151840 Hom.: 14883 Cov.: 32 AF XY: 0.440 AC XY: 32613 AN XY: 74180

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.521

Gnomad4 NFE AF: 0.460

Gnomad4 OTH AF: 0.406

Alfa AF: 0.451 Hom.: 1983

Bravo AF: 0.437

Asia WGS AF: 0.313 AC: 1096 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.7
DANN	Benign	0.61

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: rs1043582; hg19: chr2-220415646; COSMIC: COSV54706169; COSMIC: COSV54706169;