rs16996648

Positions:

• chr22-36296706-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002473.6(MYH9):​c.3272+137A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0297 in 1,011,364 control chromosomes in the GnomAD database, including 2,634 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.087 (1610 hom., cov: 32)
  • Exomes 𝑓: 0.019 (1024 hom.)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.39

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=-0.92).
• BP6: Variant 22-36296706-T-C is Benign according to our data. Variant chr22-36296706-T-C is described in ClinVar as [Benign]. Clinvar id is 1235000.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH9	NM_002473.6	c.3272+137A>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.3272+137A>G		intron_variant		1	NM_002473.6	ENSP00000216181.6
MYH9	ENST00000685801.1	c.3335+137A>G		intron_variant				ENSP00000510688.1
MYH9	ENST00000459960.1	n.481+137A>G		intron_variant		2
MYH9	ENST00000691109.1	n.3567+137A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0873 AC: 13277 AN: 152072 Hom.: 1607 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0392

Gnomad ASJ AF: 0.0210

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00869

Gnomad FIN AF: 0.0185

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.0589

GnomAD4 exome AF: 0.0195 AC: 16730 AN: 859174 Hom.: 1024 AF XY: 0.0184 AC XY: 7870 AN XY: 427932

Gnomad4 AFR exome AF: 0.286

Gnomad4 AMR exome AF: 0.0260

Gnomad4 ASJ exome AF: 0.0185

Gnomad4 EAS exome AF: 0.0000307

Gnomad4 SAS exome AF: 0.00954

Gnomad4 FIN exome AF: 0.0189

Gnomad4 NFE exome AF: 0.0122

Gnomad4 OTH exome AF: 0.0283

GnomAD4 genome AF: 0.0873 AC: 13290 AN: 152190 Hom.: 1610 Cov.: 32 AF XY: 0.0849 AC XY: 6318 AN XY: 74410

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.0392

Gnomad4 ASJ AF: 0.0210

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00849

Gnomad4 FIN AF: 0.0185

Gnomad4 NFE AF: 0.0130

Gnomad4 OTH AF: 0.0582

Alfa AF: 0.0585 Hom.: 279

Bravo AF: 0.0969

Asia WGS AF: 0.0190 AC: 69 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.074
DANN	Benign	0.46

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: rs16996648; hg19: chr22-36692752;