rs11913874

Variant names:

• chr22-36341658-C-G
• rs11913874
• NM_002473.6:c.334-132G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002473.6(MYH9):​c.334-132G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 1,023,528 control chromosomes in the GnomAD database, including 796 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.051 (434 hom., cov: 32)
  • Exomes 𝑓: 0.017 (362 hom.)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0660
• Publications: 2 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

ENSG00000287269 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 22-36341658-C-G is Benign according to our data. Variant chr22-36341658-C-G is described in ClinVar as Benign. ClinVar VariationId is 1274553.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 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.334-132G>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.334-132G>C		intron	N/A	ENSP00000216181.6
	MYH9	ENST00000401701.1	TSL:1	c.334-132G>C		intron	N/A	ENSP00000384631.1
	MYH9	ENST00000685801.1		c.334-132G>C		intron	N/A	ENSP00000510688.1

Frequencies

GnomAD3 genomes AF: 0.0510 AC: 7755 AN: 152146 Hom.: 434 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0384

Gnomad ASJ AF: 0.0236

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0161

Gnomad FIN AF: 0.0148

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0134

Gnomad OTH AF: 0.0493

GnomAD4 exome AF: 0.0171 AC: 14856 AN: 871264 Hom.: 362 AF XY: 0.0167 AC XY: 7511 AN XY: 449596

African (AFR) AF: 0.140 AC: 2924 AN: 20930

American (AMR) AF: 0.0219 AC: 773 AN: 35276

Ashkenazi Jewish (ASJ) AF: 0.0205 AC: 442 AN: 21560

East Asian (EAS) AF: 0.000154 AC: 5 AN: 32392

South Asian (SAS) AF: 0.0180 AC: 1257 AN: 69808

European-Finnish (FIN) AF: 0.0165 AC: 546 AN: 33152

Middle Eastern (MID) AF: 0.0824 AC: 289 AN: 3506

European-Non Finnish (NFE) AF: 0.0122 AC: 7521 AN: 614018

Other (OTH) AF: 0.0271 AC: 1099 AN: 40622

GnomAD4 genome AF: 0.0511 AC: 7777 AN: 152264 Hom.: 434 Cov.: 32 AF XY: 0.0495 AC XY: 3683 AN XY: 74462

African (AFR) AF: 0.140 AC: 5832 AN: 41516

American (AMR) AF: 0.0384 AC: 588 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0236 AC: 82 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5188

South Asian (SAS) AF: 0.0157 AC: 76 AN: 4828

European-Finnish (FIN) AF: 0.0148 AC: 157 AN: 10608

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

European-Non Finnish (NFE) AF: 0.0134 AC: 910 AN: 68034

Other (OTH) AF: 0.0493 AC: 104 AN: 2110

Alfa AF: 0.0367 Hom.: 41

Bravo AF: 0.0559

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.2
DANN	Benign	0.48
PhyloP100		-0.066
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: rs11913874; hg19: chr22-36737703;