2-219551112-A-G

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.5684-270T>C 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 1,402,120 control chromosomes in the GnomAD database, including 680,020 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.94 (67965 hom., cov: 31)
  • Exomes 𝑓: 0.99 (612055 hom.)
• Consequence: OBSL1 NM_015311.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.49

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=-0.88).
• BP6: Variant 2-219551112-A-G is Benign according to our data. Variant chr2-219551112-A-G is described in ClinVar as [Benign]. Clinvar id is 1234756.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.5684-270T>C		intron_variant		ENST00000404537.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OBSL1	ENST00000404537.6	c.5684-270T>C		intron_variant		1	NM_015311.3	P1

Frequencies

GnomAD3 genomes AF: 0.942 AC: 143251 AN: 152026 Hom.: 67939 Cov.: 31

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.952

Gnomad AMR AF: 0.965

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: 0.955

GnomAD4 exome AF: 0.989 AC: 1236402 AN: 1249976 Hom.: 612055 Cov.: 44 AF XY: 0.990 AC XY: 597141 AN XY: 603372

Gnomad4 AFR exome AF: 0.803

Gnomad4 AMR exome AF: 0.978

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: 0.980

GnomAD4 genome AF: 0.942 AC: 143333 AN: 152144 Hom.: 67965 Cov.: 31 AF XY: 0.943 AC XY: 70140 AN XY: 74376

Gnomad4 AFR AF: 0.817

Gnomad4 AMR AF: 0.965

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: 0.955

Alfa AF: 0.963 Hom.: 8810

Bravo AF: 0.935

Asia WGS AF: 0.983 AC: 3419 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	-0.88
Cadd	Benign	0.80
Dann	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6717394; hg19: chr2-220415834;