rs1002246

Variant names:

• chr22-36318614-G-A
• rs1002246
• NM_002473.6:c.1109-289C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-36318614-G-A
• chr22-36318614-G-C
• chr22-36318614-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.1109-289C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,922 control chromosomes in the GnomAD database, including 14,066 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.41 (14066 hom., cov: 32)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.03
• Publications: 3 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

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 22-36318614-G-A is Benign according to our data. Variant chr22-36318614-G-A is described in ClinVar as Benign. ClinVar VariationId is 1228453.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH9	NM_002473.6	c.1109-289C>T		intron_variant	Intron 10 of 40	ENST00000216181.11	NP_002464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11	c.1109-289C>T		intron_variant	Intron 10 of 40	1	NM_002473.6	ENSP00000216181.6

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62780 AN: 151804 Hom.: 14035 Cov.: 32

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.414 AC: 62867 AN: 151922 Hom.: 14066 Cov.: 32 AF XY: 0.420 AC XY: 31166 AN XY: 74236

African (AFR) AF: 0.532 AC: 22036 AN: 41396

American (AMR) AF: 0.352 AC: 5376 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1318 AN: 3462

East Asian (EAS) AF: 0.758 AC: 3891 AN: 5132

South Asian (SAS) AF: 0.581 AC: 2795 AN: 4812

European-Finnish (FIN) AF: 0.383 AC: 4044 AN: 10560

Middle Eastern (MID) AF: 0.329 AC: 96 AN: 292

European-Non Finnish (NFE) AF: 0.327 AC: 22216 AN: 67952

Other (OTH) AF: 0.403 AC: 852 AN: 2114

Alfa AF: 0.369 Hom.: 19433

Bravo AF: 0.412

Asia WGS AF: 0.699 AC: 2431 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.15
DANN	Benign	0.44
PhyloP100		-1.0
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: rs1002246; hg19: chr22-36714659;