22-36284668-C-T

Position:

• chr22-36284668-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002473.6(MYH9):​c.5484-157G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0411 in 152,208 control chromosomes in the GnomAD database, including 133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.041 (133 hom., cov: 33)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.871

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]

MYH9 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 22-36284668-C-T is Benign according to our data. Variant chr22-36284668-C-T is described in ClinVar as [Benign]. Clinvar id is 1225120.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH9	NM_002473.6	c.5484-157G>A		intron_variant		ENST00000216181.11	NP_002464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11	c.5484-157G>A		intron_variant		1	NM_002473.6	ENSP00000216181.6

Frequencies

GnomAD3 genomes AF: 0.0412 AC: 6262 AN: 152090 Hom.: 133 Cov.: 33

Gnomad AFR AF: 0.0271

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0204

Gnomad ASJ AF: 0.0429

Gnomad EAS AF: 0.0572

Gnomad SAS AF: 0.0539

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0509

Gnomad OTH AF: 0.0379

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

GnomAD4 genome AF: 0.0411 AC: 6263 AN: 152208 Hom.: 133 Cov.: 33 AF XY: 0.0405 AC XY: 3012 AN XY: 74398

Gnomad4 AFR AF: 0.0271

Gnomad4 AMR AF: 0.0203

Gnomad4 ASJ AF: 0.0429

Gnomad4 EAS AF: 0.0571

Gnomad4 SAS AF: 0.0535

Gnomad4 FIN AF: 0.0515

Gnomad4 NFE AF: 0.0508

Gnomad4 OTH AF: 0.0398

Alfa AF: 0.0164 Hom.: 5

Bravo AF: 0.0376

Asia WGS AF: 0.0720 AC: 248 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.097
DANN	Benign	0.66

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: rs2071732; hg19: chr22-36680714;