rs11549907

Variant names:

• chr22-36288934-G-A
• rs11549907
• NM_002473.6:c.4563C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-36288934-G-A
• chr22-36288934-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002473.6(MYH9):​c.4563C>T​(p.His1521His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 1,613,760 control chromosomes in the GnomAD database, including 727 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (178 hom., cov: 32)
  • Exomes 𝑓: 0.017 (549 hom.)
• Consequence: MYH9 NM_002473.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -0.560
• Publications: 7 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: Labcorp Genetics (formerly Invitae), G2P
• macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 22-36288934-G-A is Benign according to our data. Variant chr22-36288934-G-A is described in ClinVar as Benign. ClinVar VariationId is 44563.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.56 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.1 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH9	NM_002473.6	MANE Select	c.4563C>T	p.His1521His	synonymous	Exon 33 of 41	NP_002464.1	P35579-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH9	ENST00000216181.11	TSL:1 MANE Select	c.4563C>T	p.His1521His	synonymous	Exon 33 of 41	ENSP00000216181.6	P35579-1
	MYH9	ENST00000685801.1		c.4626C>T	p.His1542His	synonymous	Exon 34 of 42	ENSP00000510688.1	A0A8I5KWT8
	MYH9	ENST00000955568.1		c.4626C>T	p.His1542His	synonymous	Exon 34 of 42	ENSP00000625627.1

Frequencies

GnomAD3 genomes AF: 0.0356 AC: 5409 AN: 152090 Hom.: 178 Cov.: 32

Gnomad AFR AF: 0.0614

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0211

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00830

Gnomad FIN AF: 0.0184

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0127

Gnomad OTH AF: 0.0321

GnomAD2 exomes AF: 0.0284 AC: 7134 AN: 251068 AF XY: 0.0243

Gnomad AFR exome AF: 0.0605

Gnomad AMR exome AF: 0.105

Gnomad ASJ exome AF: 0.0201

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0185

Gnomad NFE exome AF: 0.0129

Gnomad OTH exome AF: 0.0328

GnomAD4 exome AF: 0.0169 AC: 24677 AN: 1461552 Hom.: 549 Cov.: 34 AF XY: 0.0161 AC XY: 11738 AN XY: 727100

African (AFR) AF: 0.0647 AC: 2165 AN: 33480

American (AMR) AF: 0.105 AC: 4676 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0193 AC: 504 AN: 26136

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.00947 AC: 817 AN: 86258

European-Finnish (FIN) AF: 0.0187 AC: 993 AN: 53086

Middle Eastern (MID) AF: 0.0766 AC: 442 AN: 5768

European-Non Finnish (NFE) AF: 0.0124 AC: 13798 AN: 1112008

Other (OTH) AF: 0.0212 AC: 1278 AN: 60392

GnomAD4 genome AF: 0.0355 AC: 5409 AN: 152208 Hom.: 178 Cov.: 32 AF XY: 0.0366 AC XY: 2722 AN XY: 74414

African (AFR) AF: 0.0613 AC: 2546 AN: 41526

American (AMR) AF: 0.104 AC: 1595 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0211 AC: 73 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.00810 AC: 39 AN: 4816

European-Finnish (FIN) AF: 0.0184 AC: 195 AN: 10606

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0127 AC: 867 AN: 68010

Other (OTH) AF: 0.0317 AC: 67 AN: 2112

Alfa AF: 0.0213 Hom.: 60

Bravo AF: 0.0414

Asia WGS AF: 0.0140 AC: 52 AN: 3478

EpiCase AF: 0.0154

EpiControl AF: 0.0151

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	4	not specified (4)
-	-	1	Atypical hemolytic-uremic syndrome (1)
-	-	1	Autosomal dominant nonsyndromic hearing loss 17 (1)
-	-	1	MYH9-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.94
DANN	Benign	0.49
PhyloP100		-0.56
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.7
Mutation Taster		=96/4	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: rs11549907; hg19: chr22-36684980; COSMIC: COSV53384859; COSMIC: COSV53384859;