chr22-36387988-C-T

Position:

• chr22-36387988-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000685801.1(MYH9):​c.-201G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 152,406 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (18 hom., cov: 32)
  • Exomes 𝑓: 0.016 (0 hom.)
• Consequence: MYH9 ENST00000685801.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.266

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=-0.68).
• BP6: Variant 22-36387988-C-T is Benign according to our data. Variant chr22-36387988-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 341542.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr22-36387988-C-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0116 (1769/152280) while in subpopulation NFE AF= 0.0179 (1218/68000). AF 95% confidence interval is 0.0171. There are 18 homozygotes in gnomad4. There are 871 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1769 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.36387988C>T		intergenic_region
MYH9	NM_002473.6	c.-201G>A		upstream_gene_variant		ENST00000216181.11	NP_002464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11	c.-201G>A		upstream_gene_variant		1	NM_002473.6	ENSP00000216181.6

Frequencies

GnomAD3 genomes AF: 0.0116 AC: 1768 AN: 152162 Hom.: 18 Cov.: 32

Gnomad AFR AF: 0.00302

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00458

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.0283

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0179

Gnomad OTH AF: 0.00813

GnomAD4 exome AF: 0.0159 AC: 2 AN: 126 Hom.: 0 Cov.: 0 AF XY: 0.0200 AC XY: 2 AN XY: 100

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0189

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0116 AC: 1769 AN: 152280 Hom.: 18 Cov.: 32 AF XY: 0.0117 AC XY: 871 AN XY: 74452

Gnomad4 AFR AF: 0.00301

Gnomad4 AMR AF: 0.00457

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00435

Gnomad4 FIN AF: 0.0283

Gnomad4 NFE AF: 0.0179

Gnomad4 OTH AF: 0.00804

Alfa AF: 0.0105 Hom.: 7

Bravo AF: 0.00926

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Nonsyndromic Hearing Loss, Dominant Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

MYH9-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	17
DANN	Benign	0.89

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: rs189394948; hg19: chr22-36784033;