2-219551442-T-C

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.5683+87A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.984 in 1,447,860 control chromosomes in the GnomAD database, including 701,902 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.94 (67572 hom., cov: 29)
  • Exomes 𝑓: 0.99 (634330 hom.)
• Consequence: OBSL1 NM_015311.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.74

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=-0.9).
• BP6: Variant 2-219551442-T-C is Benign according to our data. Variant chr2-219551442-T-C is described in ClinVar as [Benign]. Clinvar id is 1247466.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OBSL1	NM_015311.3	c.5683+87A>G		intron_variant		ENST00000404537.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OBSL1	ENST00000404537.6	c.5683+87A>G		intron_variant		1	NM_015311.3	P1

Frequencies

GnomAD3 genomes AF: 0.940 AC: 142748 AN: 151872 Hom.: 67547 Cov.: 29

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.952

Gnomad AMR AF: 0.964

Gnomad ASJ AF: 0.993

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 0.994

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.993

Gnomad OTH AF: 0.953

GnomAD4 exome AF: 0.989 AC: 1281560 AN: 1295870 Hom.: 634330 Cov.: 22 AF XY: 0.990 AC XY: 622929 AN XY: 629456

Gnomad4 AFR exome AF: 0.799

Gnomad4 AMR exome AF: 0.980

Gnomad4 ASJ exome AF: 0.995

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.999

Gnomad4 FIN exome AF: 0.994

Gnomad4 NFE exome AF: 0.994

Gnomad4 OTH exome AF: 0.979

GnomAD4 genome AF: 0.940 AC: 142828 AN: 151990 Hom.: 67572 Cov.: 29 AF XY: 0.941 AC XY: 69901 AN XY: 74296

Gnomad4 AFR AF: 0.809

Gnomad4 AMR AF: 0.964

Gnomad4 ASJ AF: 0.993

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 0.994

Gnomad4 NFE AF: 0.993

Gnomad4 OTH AF: 0.953

Alfa AF: 0.983 Hom.: 67960

Bravo AF: 0.932

Asia WGS AF: 0.982 AC: 3416 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.2
Dann	Benign	0.79

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: rs6761575; hg19: chr2-220416164;