rs5756152

chr22-36316427-A-Gchr22-36316427-A-T

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.1380+90T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.963 in 1,587,798 control chromosomes in the GnomAD database, including 739,209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.90 (62978 hom., cov: 30)
  • Exomes 𝑓: 0.97 (676231 hom.)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.319

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 22-36316427-A-G is Benign according to our data. Variant chr22-36316427-A-G is described in ClinVar as [Benign]. Clinvar id is 1256889.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH9	NM_002473.6	c.1380+90T>C		intron_variant		ENST00000216181.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH9	ENST00000216181.11	c.1380+90T>C		intron_variant		1	NM_002473.6	P1

Frequencies

GnomAD3 genomes AF: 0.904 AC: 137182 AN: 151752 Hom.: 62929 Cov.: 30

Gnomad AFR AF: 0.726

Gnomad AMI AF: 0.995

Gnomad AMR AF: 0.960

Gnomad ASJ AF: 0.958

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.985

Gnomad FIN AF: 0.963

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.972

Gnomad OTH AF: 0.928

GnomAD4 exome AF: 0.970 AC: 1392309 AN: 1435928 Hom.: 676231 AF XY: 0.970 AC XY: 694808 AN XY: 715934

Gnomad4 AFR exome AF: 0.712

Gnomad4 AMR exome AF: 0.977

Gnomad4 ASJ exome AF: 0.961

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.986

Gnomad4 FIN exome AF: 0.963

Gnomad4 NFE exome AF: 0.976

Gnomad4 OTH exome AF: 0.963

GnomAD4 genome AF: 0.904 AC: 137288 AN: 151870 Hom.: 62978 Cov.: 30 AF XY: 0.906 AC XY: 67259 AN XY: 74212

Gnomad4 AFR AF: 0.726

Gnomad4 AMR AF: 0.961

Gnomad4 ASJ AF: 0.958

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.986

Gnomad4 FIN AF: 0.963

Gnomad4 NFE AF: 0.972

Gnomad4 OTH AF: 0.929

Alfa AF: 0.959 Hom.: 67913

Bravo AF: 0.897

Asia WGS AF: 0.974 AC: 3386 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

Jun 22, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.0
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: rs5756152; hg19: chr22-36712472;