rs5756129

Variant names:

• chr22-36288046-T-C
• rs5756129
• NM_002473.6:c.4932+206A>G

Your query was ambiguous. Multiple possible variants found:

• chr22-36288046-T-C
• chr22-36288046-T-A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002473.6(MYH9):​c.4932+206A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,100 control chromosomes in the GnomAD database, including 6,176 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.26 (6176 hom., cov: 32)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.271
• Publications: 23 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 22-36288046-T-C is Benign according to our data. Variant chr22-36288046-T-C is described in ClinVar as Benign. ClinVar VariationId is 1288550.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.683 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.4932+206A>G		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.4932+206A>G		intron	N/A	ENSP00000216181.6	P35579-1
	MYH9	ENST00000685801.1		c.4995+206A>G		intron	N/A	ENSP00000510688.1	A0A8I5KWT8
	MYH9	ENST00000955568.1		c.4995+206A>G		intron	N/A	ENSP00000625627.1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 40030 AN: 151982 Hom.: 6159 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.264 AC: 40082 AN: 152100 Hom.: 6176 Cov.: 32 AF XY: 0.272 AC XY: 20197 AN XY: 74338

African (AFR) AF: 0.194 AC: 8055 AN: 41512

American (AMR) AF: 0.336 AC: 5138 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1339 AN: 3472

East Asian (EAS) AF: 0.702 AC: 3607 AN: 5140

South Asian (SAS) AF: 0.526 AC: 2537 AN: 4822

European-Finnish (FIN) AF: 0.240 AC: 2532 AN: 10570

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.235 AC: 15968 AN: 67988

Other (OTH) AF: 0.295 AC: 625 AN: 2116

Alfa AF: 0.256 Hom.: 8878

Bravo AF: 0.268

Asia WGS AF: 0.596 AC: 2069 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.42
DANN	Benign	0.66
PhyloP100		-0.27
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: rs5756129; hg19: chr22-36684092;