rs876661302

Positions:

• chr22-36296899-CGCGATCTGGGCCTGGAGCTCG-C
• chr22-36296899-CGCGATCTGGGCCTGGAGCTCG-CGCGATCTGGGCCTGGAGCTCGGCGATCTGGGCCTGGAGCTCG

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2 PP3 PP5 BP3

The NM_002473.6(MYH9):​c.3195_3215del​(p.Gln1068_Leu1074del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. A1065A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYH9 NM_002473.6 inframe_deletion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.97

Genes affected

MYH9 (HGNC:7579): (myosin heavy chain 9) This gene encodes a conventional non-muscle myosin; this protein should not be confused with the unconventional myosin-9a or 9b (MYO9A or MYO9B). The encoded protein is a myosin IIA heavy chain that contains an IQ domain and a myosin head-like domain which is involved in several important functions, including cytokinesis, cell motility and maintenance of cell shape. Defects in this gene have been associated with non-syndromic sensorineural deafness autosomal dominant type 17, Epstein syndrome, Alport syndrome with macrothrombocytopenia, Sebastian syndrome, Fechtner syndrome and macrothrombocytopenia with progressive sensorineural deafness. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
• PP5: Variant 22-36296899-CGCGATCTGGGCCTGGAGCTCG-C is Pathogenic according to our data. Variant chr22-36296899-CGCGATCTGGGCCTGGAGCTCG-C is described in ClinVar as [Pathogenic]. Clinvar id is 14084.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr22-36296899-CGCGATCTGGGCCTGGAGCTCG-C is described in Lovd as [Pathogenic]. Variant chr22-36296899-CGCGATCTGGGCCTGGAGCTCG-C is described in Lovd as [Pathogenic].
• BP3: Nonframeshift variant in repetitive region in NM_002473.6

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH9	NM_002473.6	c.3195_3215del	p.Gln1068_Leu1074del	inframe_deletion	25/41	ENST00000216181.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH9	ENST00000216181.11	c.3195_3215del	p.Gln1068_Leu1074del	inframe_deletion	25/41	1	NM_002473.6	P1
MYH9	ENST00000685801.1	c.3258_3278del	p.Gln1089_Leu1095del	inframe_deletion	26/42
MYH9	ENST00000459960.1	n.404_424del		non_coding_transcript_exon_variant	1/2	2
MYH9	ENST00000691109.1	n.3490_3510del		non_coding_transcript_exon_variant	19/35

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: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 01, 2009

- -

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: rs876661302; hg19: chr22-36692945;