chr22-36368743-A-G

Variant names:

• chr22-36368743-A-G
• rs16996704
• NM_002473.6:c.-20+19064T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002473.6(MYH9):​c.-20+19064T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 151,918 control chromosomes in the GnomAD database, including 4,916 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (4916 hom., cov: 31)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 17

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
• May-Hegglin anomaly

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002473.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH9	NM_002473.6	MANE Select	c.-20+19064T>C		intron	N/A	NP_002464.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH9	ENST00000216181.11	TSL:1 MANE Select	c.-20+19064T>C		intron	N/A	ENSP00000216181.6
	MYH9	ENST00000685801.1		c.-20+19064T>C		intron	N/A	ENSP00000510688.1
	MYH9	ENST00000688137.1		c.-20+1843T>C		intron	N/A	ENSP00000510189.1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33065 AN: 151800 Hom.: 4897 Cov.: 31

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.0956

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.188

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.218 AC: 33137 AN: 151918 Hom.: 4916 Cov.: 31 AF XY: 0.217 AC XY: 16106 AN XY: 74290

African (AFR) AF: 0.428 AC: 17700 AN: 41372

American (AMR) AF: 0.182 AC: 2776 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0956 AC: 331 AN: 3462

East Asian (EAS) AF: 0.109 AC: 564 AN: 5164

South Asian (SAS) AF: 0.117 AC: 565 AN: 4822

European-Finnish (FIN) AF: 0.168 AC: 1775 AN: 10564

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8840 AN: 67962

Other (OTH) AF: 0.187 AC: 395 AN: 2108

Alfa AF: 0.155 Hom.: 2219

Bravo AF: 0.229

Asia WGS AF: 0.157 AC: 545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.7
DANN	Benign	0.79
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16996704; hg19: chr22-36764788;