rs17806513

Positions:

• chr22-36304340-G-A

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.2230-185C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0379 in 152,192 control chromosomes in the GnomAD database, including 213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.038 (213 hom., cov: 33)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0160

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=-0.85).
• BP6: Variant 22-36304340-G-A is Benign according to our data. Variant chr22-36304340-G-A is described in ClinVar as [Benign]. Clinvar id is 1251305.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH9	NM_002473.6	c.2230-185C>T		intron_variant		ENST00000216181.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH9	ENST00000216181.11	c.2230-185C>T		intron_variant		1	NM_002473.6	P1
MYH9	ENST00000685801.1	c.2293-185C>T		intron_variant
MYH9	ENST00000691109.1	n.2525-185C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0379 AC: 5757 AN: 152074 Hom.: 212 Cov.: 33

Gnomad AFR AF: 0.0962

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0315

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00890

Gnomad FIN AF: 0.0184

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.0349

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

GnomAD4 genome AF: 0.0379 AC: 5769 AN: 152192 Hom.: 213 Cov.: 33 AF XY: 0.0375 AC XY: 2792 AN XY: 74418

Gnomad4 AFR AF: 0.0962

Gnomad4 AMR AF: 0.0315

Gnomad4 ASJ AF: 0.0213

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00870

Gnomad4 FIN AF: 0.0184

Gnomad4 NFE AF: 0.0130

Gnomad4 OTH AF: 0.0345

Alfa AF: 0.0285 Hom.: 16

Bravo AF: 0.0405

Asia WGS AF: 0.0150 AC: 53 AN: 3478

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	Oct 01, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.3
DANN	Benign	0.61

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: rs17806513; hg19: chr22-36700386;