rs5756142

chr22-36314011-A-G

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.1554+134T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 1,187,618 control chromosomes in the GnomAD database, including 232,022 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.53 (23666 hom., cov: 31)
  • Exomes 𝑓: 0.62 (208356 hom.)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.57

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=-0.9).
• BP6: Variant 22-36314011-A-G is Benign according to our data. Variant chr22-36314011-A-G is described in ClinVar as [Benign]. Clinvar id is 1227147.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH9	NM_002473.6	c.1554+134T>C		intron_variant		ENST00000216181.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH9	ENST00000216181.11	c.1554+134T>C		intron_variant		1	NM_002473.6	P1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 79910 AN: 151692 Hom.: 23672 Cov.: 31

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.550

GnomAD4 exome AF: 0.620 AC: 642611 AN: 1035810 Hom.: 208356 AF XY: 0.614 AC XY: 322103 AN XY: 524694

Gnomad4 AFR exome AF: 0.249

Gnomad4 AMR exome AF: 0.632

Gnomad4 ASJ exome AF: 0.529

Gnomad4 EAS exome AF: 0.217

Gnomad4 SAS exome AF: 0.414

Gnomad4 FIN exome AF: 0.653

Gnomad4 NFE exome AF: 0.675

Gnomad4 OTH exome AF: 0.578

GnomAD4 genome AF: 0.526 AC: 79909 AN: 151808 Hom.: 23666 Cov.: 31 AF XY: 0.522 AC XY: 38708 AN XY: 74176

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.610

Gnomad4 ASJ AF: 0.527

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.651

Gnomad4 NFE AF: 0.675

Gnomad4 OTH AF: 0.545

Alfa AF: 0.620 Hom.: 6049

Bravo AF: 0.515

Asia WGS AF: 0.255 AC: 887 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 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.45
Dann	Benign	0.37

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: rs5756142; hg19: chr22-36710056;