rs8136069

Positions:

• chr22-36326445-C-A
• chr22-36326445-C-T

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.612+123G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 948,970 control chromosomes in the GnomAD database, including 72,700 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9678 hom., cov: 33)
  • Exomes 𝑓: 0.38 (63022 hom.)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.866

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=-0.58).
• BP6: Variant 22-36326445-C-A is Benign according to our data. Variant chr22-36326445-C-A is described in ClinVar as [Benign]. Clinvar id is 1232746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH9	NM_002473.6	c.612+123G>T		intron_variant		ENST00000216181.11	NP_002464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11	c.612+123G>T		intron_variant		1	NM_002473.6	ENSP00000216181	P1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51558 AN: 152026 Hom.: 9655 Cov.: 33

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.342

Gnomad OTH AF: 0.361

GnomAD4 exome AF: 0.379 AC: 302033 AN: 796826 Hom.: 63022 AF XY: 0.387 AC XY: 163129 AN XY: 421794

Gnomad4 AFR exome AF: 0.245

Gnomad4 AMR exome AF: 0.341

Gnomad4 ASJ exome AF: 0.442

Gnomad4 EAS exome AF: 0.816

Gnomad4 SAS exome AF: 0.526

Gnomad4 FIN exome AF: 0.323

Gnomad4 NFE exome AF: 0.338

Gnomad4 OTH exome AF: 0.382

GnomAD4 genome AF: 0.339 AC: 51613 AN: 152144 Hom.: 9678 Cov.: 33 AF XY: 0.345 AC XY: 25656 AN XY: 74380

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.333

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.827

Gnomad4 SAS AF: 0.560

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.342

Gnomad4 OTH AF: 0.366

Alfa AF: 0.354 Hom.: 19433

Bravo AF: 0.334

Asia WGS AF: 0.670 AC: 2328 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	Jul 27, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.84

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: rs8136069; hg19: chr22-36722490;