rs136206

chr22-36359453-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002473.6(MYH9):c.-19-10198T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 152,134 control chromosomes in the GnomAD database, including 26,654 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.57 (26654 hom., cov: 33)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.818

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH9	NM_002473.6	c.-19-10198T>C		intron_variant		ENST00000216181.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH9	ENST00000216181.11	c.-19-10198T>C		intron_variant		1	NM_002473.6	P1

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86931 AN: 152016 Hom.: 26651 Cov.: 33

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.649

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.572 AC: 86967 AN: 152134 Hom.: 26654 Cov.: 33 AF XY: 0.562 AC XY: 41836 AN XY: 74382

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.592

Gnomad4 ASJ AF: 0.581

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.649

Gnomad4 NFE AF: 0.704

Gnomad4 OTH AF: 0.593

Alfa AF: 0.665 Hom.: 63544

Bravo AF: 0.561

Asia WGS AF: 0.270 AC: 939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.24
Dann	Benign	0.28

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: rs136206; hg19: chr22-36755498;