rs56063322

chr22-36295107-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002473.6(MYH9):c.3486-31G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00549 in 1,613,990 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0049 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0055 (36 hom.)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0820

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=-0.8).
• BP6: Variant 22-36295107-C-G is Benign according to our data. Variant chr22-36295107-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 258742.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00493 (751/152296) while in subpopulation NFE AF= 0.00578 (393/68024). AF 95% confidence interval is 0.00531. There are 5 homozygotes in gnomad4. There are 447 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 750 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH9	NM_002473.6	c.3486-31G>C		intron_variant		ENST00000216181.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH9	ENST00000216181.11	c.3486-31G>C		intron_variant		1	NM_002473.6	P1
MYH9	ENST00000685801.1	c.3549-31G>C		intron_variant
MYH9	ENST00000691109.1	n.3781-31G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00493 AC: 750 AN: 152178 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00578

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00560 AC: 1407 AN: 251262 Hom.: 8 AF XY: 0.00574 AC XY: 779 AN XY: 135828

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.000665

Gnomad ASJ exome AF: 0.00139

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00242

Gnomad FIN exome AF: 0.0269

Gnomad NFE exome AF: 0.00598

Gnomad OTH exome AF: 0.00473

GnomAD4 exome AF: 0.00554 AC: 8103 AN: 1461694 Hom.: 36 Cov.: 32 AF XY: 0.00558 AC XY: 4055 AN XY: 727168

Gnomad4 AFR exome AF: 0.000478

Gnomad4 AMR exome AF: 0.000626

Gnomad4 ASJ exome AF: 0.00130

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00236

Gnomad4 FIN exome AF: 0.0264

Gnomad4 NFE exome AF: 0.00552

Gnomad4 OTH exome AF: 0.00447

GnomAD4 genome AF: 0.00493 AC: 751 AN: 152296 Hom.: 5 Cov.: 33 AF XY: 0.00600 AC XY: 447 AN XY: 74472

Gnomad4 AFR AF: 0.000602

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.0283

Gnomad4 NFE AF: 0.00578

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00434 Hom.: 0

Bravo AF: 0.00270

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	7.3
Dann	Benign	0.60
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: rs56063322; hg19: chr22-36691153;