rs1553601860

Positions:

• chr2-151694639-AAAA-AT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001164507.2(NEB):​c.1675-13_1675-11delinsA variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NEB NM_001164507.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.81

Genes affected

NEB (HGNC:7720): (nebulin) This gene encodes nebulin, a giant protein component of the cytoskeletal matrix that coexists with the thick and thin filaments within the sarcomeres of skeletal muscle. In most vertebrates, nebulin accounts for 3 to 4% of the total myofibrillar protein. The encoded protein contains approximately 30-amino acid long modules that can be classified into 7 types and other repeated modules. Protein isoform sizes vary from 600 to 800 kD due to alternative splicing that is tissue-, species-,and developmental stage-specific. Of the 183 exons in the nebulin gene, at least 43 are alternatively spliced, although exons 143 and 144 are not found in the same transcript. Of the several thousand transcript variants predicted for nebulin, the RefSeq Project has decided to create three representative RefSeq records. Mutations in this gene are associated with recessive nemaline myopathy. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 2-151694640-AAA-T is Benign according to our data. Variant chr2-151694640-AAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 257768.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEB	NM_001164507.2	c.1675-13_1675-11delinsA		splice_polypyrimidine_tract_variant, intron_variant		ENST00000427231.7	NP_001157979.2
NEB	NM_001164508.2	c.1675-13_1675-11delinsA		splice_polypyrimidine_tract_variant, intron_variant		ENST00000397345.8	NP_001157980.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEB	ENST00000397345.8	c.1675-13_1675-11delinsA		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001164508.2	ENSP00000380505	P5
NEB	ENST00000427231.7	c.1675-13_1675-11delinsA		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001164507.2	ENSP00000416578	A2
NEB	ENST00000489048.1	n.574-13_574-11delinsA		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		1
NEB	ENST00000409198.5	c.1675-13_1675-11delinsA		splice_polypyrimidine_tract_variant, intron_variant		5		ENSP00000386259

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1553601860; hg19: chr2-152551154;