rs5750250

Variant names:

• chr22-36312438-G-A
• rs5750250
• NM_002473.6:c.1555-216C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-36312438-G-A
• chr22-36312438-G-T

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.1555-216C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.82 in 152,088 control chromosomes in the GnomAD database, including 54,735 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.82 (54735 hom., cov: 31)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.246
• Publications: 24 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=-0.86).
• BP6: Variant 22-36312438-G-A is Benign according to our data. Variant chr22-36312438-G-A is described in ClinVar as Benign. ClinVar VariationId is 1251187.Status of the report is criteria_provided_single_submitter, 1 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.1555-216C>T		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.1555-216C>T		intron	N/A	ENSP00000216181.6	P35579-1
	MYH9	ENST00000685801.1		c.1555-216C>T		intron	N/A	ENSP00000510688.1	A0A8I5KWT8
	MYH9	ENST00000955568.1		c.1555-216C>T		intron	N/A	ENSP00000625627.1

Frequencies

GnomAD3 genomes AF: 0.820 AC: 124660 AN: 151970 Hom.: 54708 Cov.: 31

Gnomad AFR AF: 0.470

Gnomad AMI AF: 0.990

Gnomad AMR AF: 0.913

Gnomad ASJ AF: 0.936

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.976

Gnomad FIN AF: 0.945

Gnomad MID AF: 0.841

Gnomad NFE AF: 0.959

Gnomad OTH AF: 0.864

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

GnomAD4 genome AF: 0.820 AC: 124737 AN: 152088 Hom.: 54735 Cov.: 31 AF XY: 0.824 AC XY: 61284 AN XY: 74336

African (AFR) AF: 0.470 AC: 19458 AN: 41396

American (AMR) AF: 0.913 AC: 13958 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.936 AC: 3251 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5161 AN: 5166

South Asian (SAS) AF: 0.976 AC: 4706 AN: 4820

European-Finnish (FIN) AF: 0.945 AC: 10013 AN: 10600

Middle Eastern (MID) AF: 0.846 AC: 247 AN: 292

European-Non Finnish (NFE) AF: 0.959 AC: 65213 AN: 68026

Other (OTH) AF: 0.865 AC: 1827 AN: 2112

Alfa AF: 0.913 Hom.: 81518

Bravo AF: 0.802

Asia WGS AF: 0.953 AC: 3311 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	-0.86
CADD	Benign	0.90
DANN	Benign	0.53
PhyloP100		-0.25
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: rs5750250; hg19: chr22-36708483;