rs1557529

Positions:

• chr22-36309484-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000216181.11(MYH9):​c.1729-88T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.951 in 961,442 control chromosomes in the GnomAD database, including 438,242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.88 (60517 hom., cov: 33)
  • Exomes 𝑓: 0.96 (377725 hom.)
• Consequence: MYH9 ENST00000216181.11 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0880

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 22-36309484-A-G is Benign according to our data. Variant chr22-36309484-A-G is described in ClinVar as [Benign]. Clinvar id is 1286206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH9	NM_002473.6	c.1729-88T>C		intron_variant		ENST00000216181.11	NP_002464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11	c.1729-88T>C		intron_variant		1	NM_002473.6	ENSP00000216181	P1

Frequencies

GnomAD3 genomes AF: 0.879 AC: 133769 AN: 152134 Hom.: 60471 Cov.: 33

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.995

Gnomad AMR AF: 0.954

Gnomad ASJ AF: 0.958

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.984

Gnomad FIN AF: 0.963

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.971

Gnomad OTH AF: 0.911

GnomAD4 exome AF: 0.965 AC: 780513 AN: 809190 Hom.: 377725 AF XY: 0.967 AC XY: 411006 AN XY: 425180

Gnomad4 AFR exome AF: 0.633

Gnomad4 AMR exome AF: 0.972

Gnomad4 ASJ exome AF: 0.962

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.985

Gnomad4 FIN exome AF: 0.963

Gnomad4 NFE exome AF: 0.973

Gnomad4 OTH exome AF: 0.955

GnomAD4 genome AF: 0.879 AC: 133867 AN: 152252 Hom.: 60517 Cov.: 33 AF XY: 0.882 AC XY: 65684 AN XY: 74464

Gnomad4 AFR AF: 0.641

Gnomad4 AMR AF: 0.954

Gnomad4 ASJ AF: 0.958

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.985

Gnomad4 FIN AF: 0.963

Gnomad4 NFE AF: 0.971

Gnomad4 OTH AF: 0.912

Alfa AF: 0.903 Hom.: 9509

Bravo AF: 0.869

Asia WGS AF: 0.970 AC: 3373 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 15, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 80% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 74. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1557529; hg19: chr22-36705529;