rs5750248

Positions:

• chr22-36306846-T-C

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.1844-239A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 152,156 control chromosomes in the GnomAD database, including 54,248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.81 (54248 hom., cov: 32)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.25

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 22-36306846-T-C is Benign according to our data. Variant chr22-36306846-T-C is described in ClinVar as [Benign]. Clinvar id is 1238026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH9	NM_002473.6	c.1844-239A>G		intron_variant		ENST00000216181.11	NP_002464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11	c.1844-239A>G		intron_variant		1	NM_002473.6	ENSP00000216181.6
MYH9	ENST00000685801.1	c.1907-239A>G		intron_variant				ENSP00000510688.1
MYH9	ENST00000687922.1	n.180-239A>G		intron_variant
MYH9	ENST00000691109.1	n.2139-239A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.814 AC: 123705 AN: 152038 Hom.: 54225 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.990

Gnomad AMR AF: 0.911

Gnomad ASJ AF: 0.936

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.975

Gnomad FIN AF: 0.945

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.959

Gnomad OTH AF: 0.862

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

GnomAD4 genome AF: 0.813 AC: 123774 AN: 152156 Hom.: 54248 Cov.: 32 AF XY: 0.818 AC XY: 60849 AN XY: 74410

Gnomad4 AFR AF: 0.447

Gnomad4 AMR AF: 0.911

Gnomad4 ASJ AF: 0.936

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.976

Gnomad4 FIN AF: 0.945

Gnomad4 NFE AF: 0.959

Gnomad4 OTH AF: 0.864

Alfa AF: 0.893 Hom.: 13037

Bravo AF: 0.795

ClinVar

Significance: Benign

Submissions summary: Benign:2

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 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0040
DANN	Benign	0.25

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: rs5750248; hg19: chr22-36702892;