22-36316427-A-G

Variant names:

• chr22-36316427-A-G
• rs5756152
• NM_002473.6:c.1380+90T>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.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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.319
• Publications: 22 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 -20 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 VariationId is 1256889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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.1380+90T>C		intron	N/A	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.1380+90T>C		intron	N/A	ENSP00000216181.6	P35579-1
	MYH9	ENST00000685801.1		c.1380+90T>C		intron	N/A	ENSP00000510688.1	A0A8I5KWT8
	MYH9	ENST00000955568.1		c.1380+90T>C		intron	N/A	ENSP00000625627.1

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

African (AFR) AF: 0.712 AC: 23425 AN: 32900

American (AMR) AF: 0.977 AC: 43661 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.961 AC: 24941 AN: 25962

East Asian (EAS) AF: 1.00 AC: 39577 AN: 39592

South Asian (SAS) AF: 0.986 AC: 84207 AN: 85438

European-Finnish (FIN) AF: 0.963 AC: 51112 AN: 53080

Middle Eastern (MID) AF: 0.935 AC: 5344 AN: 5714

European-Non Finnish (NFE) AF: 0.976 AC: 1062708 AN: 1089048

Other (OTH) AF: 0.963 AC: 57334 AN: 59510

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

African (AFR) AF: 0.726 AC: 30047 AN: 41374

American (AMR) AF: 0.961 AC: 14670 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.958 AC: 3323 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5168 AN: 5172

South Asian (SAS) AF: 0.986 AC: 4747 AN: 4816

European-Finnish (FIN) AF: 0.963 AC: 10109 AN: 10496

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.972 AC: 66083 AN: 67956

Other (OTH) AF: 0.929 AC: 1958 AN: 2108

Alfa AF: 0.950 Hom.: 87528

Bravo AF: 0.897

Asia WGS AF: 0.974 AC: 3386 AN: 3478

ClinVar

ClinVar submissions

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	-0.88
CADD	Benign	2.0
DANN	Benign	0.61
PhyloP100		-0.32
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: rs5756152; hg19: chr22-36712472;