chr2-219551442-T-C

Variant names:

• chr2-219551442-T-C
• rs6761575
• NM_015311.3:c.5683+87A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.74
• Publications: 5 publications found

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]

OBSL1 Gene-Disease associations (from GenCC):

• 3M syndrome 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• 3-M syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1247466.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015311.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OBSL1	NM_015311.3	MANE Select	c.5683+87A>G		intron	N/A	NP_056126.1	O75147-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OBSL1	ENST00000404537.6	TSL:1 MANE Select	c.5683+87A>G		intron	N/A	ENSP00000385636.1	O75147-3
	OBSL1	ENST00000953546.1		c.5695+87A>G		intron	N/A	ENSP00000623605.1
	OBSL1	ENST00000953548.1		c.5626+87A>G		intron	N/A	ENSP00000623607.1

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

African (AFR) AF: 0.799 AC: 23354 AN: 29220

American (AMR) AF: 0.980 AC: 27342 AN: 27902

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 20334 AN: 20428

East Asian (EAS) AF: 1.00 AC: 34727 AN: 34728

South Asian (SAS) AF: 0.999 AC: 66412 AN: 66474

European-Finnish (FIN) AF: 0.994 AC: 42160 AN: 42412

Middle Eastern (MID) AF: 0.977 AC: 3652 AN: 3738

European-Non Finnish (NFE) AF: 0.994 AC: 1010991 AN: 1017278

Other (OTH) AF: 0.979 AC: 52588 AN: 53690

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

African (AFR) AF: 0.809 AC: 33477 AN: 41388

American (AMR) AF: 0.964 AC: 14739 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.993 AC: 3446 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5133 AN: 5134

South Asian (SAS) AF: 0.999 AC: 4811 AN: 4814

European-Finnish (FIN) AF: 0.994 AC: 10527 AN: 10590

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.993 AC: 67537 AN: 67990

Other (OTH) AF: 0.953 AC: 2009 AN: 2108

Alfa AF: 0.977 Hom.: 87121

Bravo AF: 0.932

Asia WGS AF: 0.982 AC: 3416 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.79
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6761575; hg19: chr2-220416164;