rs770925540

Positions:

• chr22-36288741-GCTT-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PM4_Supporting BS2

The NM_002473.6(MYH9):​c.4753_4755del​(p.Lys1585del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.00000826 in 1,452,164 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000083 (0 hom.)
• Consequence: MYH9 NM_002473.6 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.08

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 Likely_benign. Variant got -3 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_002473.6. Strenght limited to Supporting due to length of the change: 1aa.
• BS2: High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH9	NM_002473.6	c.4753_4755del	p.Lys1585del	inframe_deletion	33/41	ENST00000216181.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH9	ENST00000216181.11	c.4753_4755del	p.Lys1585del	inframe_deletion	33/41	1	NM_002473.6	P1
MYH9	ENST00000685801.1	c.4816_4818del	p.Lys1606del	inframe_deletion	34/42
MYH9	ENST00000691109.1	n.5048_5050del		non_coding_transcript_exon_variant	27/35

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000412 AC: 1 AN: 242890 Hom.: 0 AF XY: 0.00000758 AC XY: 1 AN XY: 131852

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000896

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000826 AC: 12 AN: 1452164 Hom.: 0 AF XY: 0.00000692 AC XY: 5 AN XY: 722828

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal dominant nonsyndromic hearing loss 17 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Dec 18, 2017

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs770925540; hg19: chr22-36684787;