22-36299201-G-T

Variant names:

• chr22-36299201-G-T
• rs4821480
• NM_002473.6:c.2977-159C>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002473.6(MYH9):​c.2977-159C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 152,092 control chromosomes in the GnomAD database, including 52,774 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.79 (52774 hom., cov: 31)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.283

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 22-36299201-G-T is Benign according to our data. Variant chr22-36299201-G-T is described in ClinVar as [Benign]. Clinvar id is 1265122.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH9	NM_002473.6	c.2977-159C>A		intron_variant	Intron 23 of 40	ENST00000216181.11	NP_002464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11	c.2977-159C>A		intron_variant	Intron 23 of 40	1	NM_002473.6	ENSP00000216181.6
MYH9	ENST00000685801.1	c.3040-159C>A		intron_variant	Intron 24 of 41			ENSP00000510688.1
MYH9	ENST00000691109.1	n.3272-159C>A		intron_variant	Intron 17 of 34

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120327 AN: 151974 Hom.: 52761 Cov.: 31

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.990

Gnomad AMR AF: 0.905

Gnomad ASJ AF: 0.927

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.973

Gnomad FIN AF: 0.944

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.958

Gnomad OTH AF: 0.843

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

GnomAD4 genome AF: 0.791 AC: 120379 AN: 152092 Hom.: 52774 Cov.: 31 AF XY: 0.797 AC XY: 59261 AN XY: 74368

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.905

Gnomad4 ASJ AF: 0.927

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.973

Gnomad4 FIN AF: 0.944

Gnomad4 NFE AF: 0.958

Gnomad4 OTH AF: 0.845

Alfa AF: 0.860 Hom.: 7232

Bravo AF: 0.770

Asia WGS AF: 0.943 AC: 3279 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 20124285) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.2
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs4821480; hg19: chr22-36695247;