rs8136336

Positions:

• chr22-36326489-G-A
• chr22-36326489-G-C
• chr22-36326489-G-T

Variant summary

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

The NM_002473.6(MYH9):​c.612+79C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.987 in 1,277,416 control chromosomes in the GnomAD database, including 622,659 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (73742 hom., cov: 34)
  • Exomes 𝑓: 0.99 (548917 hom.)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.525

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=-0.89).
• BP6: Variant 22-36326489-G-A is Benign according to our data. Variant chr22-36326489-G-A is described in ClinVar as [Benign]. Clinvar id is 1291297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH9	NM_002473.6	c.612+79C>T		intron_variant		ENST00000216181.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH9	ENST00000216181.11	c.612+79C>T		intron_variant		1	NM_002473.6	P1

Frequencies

GnomAD3 genomes AF: 0.984 AC: 149779 AN: 152254 Hom.: 73683 Cov.: 34

Gnomad AFR AF: 0.971

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.987

Gnomad ASJ AF: 0.973

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.991

Gnomad FIN AF: 0.998

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.987

Gnomad OTH AF: 0.983

GnomAD4 exome AF: 0.988 AC: 1111304 AN: 1125044 Hom.: 548917 AF XY: 0.988 AC XY: 568618 AN XY: 575612

Gnomad4 AFR exome AF: 0.971

Gnomad4 AMR exome AF: 0.992

Gnomad4 ASJ exome AF: 0.975

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.992

Gnomad4 FIN exome AF: 0.997

Gnomad4 NFE exome AF: 0.987

Gnomad4 OTH exome AF: 0.986

GnomAD4 genome AF: 0.984 AC: 149897 AN: 152372 Hom.: 73742 Cov.: 34 AF XY: 0.984 AC XY: 73334 AN XY: 74514

Gnomad4 AFR AF: 0.971

Gnomad4 AMR AF: 0.988

Gnomad4 ASJ AF: 0.973

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.991

Gnomad4 FIN AF: 0.998

Gnomad4 NFE AF: 0.987

Gnomad4 OTH AF: 0.983

Alfa AF: 0.985 Hom.: 19073

Bravo AF: 0.983

Asia WGS AF: 0.992 AC: 3449 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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 90% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 84. Only high quality variants are reported. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.34
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs8136336; hg19: chr22-36722534;