chr22-36310226-T-C

Position:

• chr22-36310226-T-C

Variant summary

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

The NM_002473.6(MYH9):​c.1729-830A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 149,972 control chromosomes in the GnomAD database, including 25,877 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 0.56 (25877 hom., cov: 26)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH9	NM_002473.6	c.1729-830A>G		intron_variant		ENST00000216181.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH9	ENST00000216181.11	c.1729-830A>G		intron_variant		1	NM_002473.6	P1
MYH9	ENST00000685801.1	c.1729-830A>G		intron_variant
MYH9	ENST00000691109.1	n.2024-830A>G		intron_variant, non_coding_transcript_variant
MYH9	ENST00000692930.1	n.1943-830A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.556 AC: 83291 AN: 149866 Hom.: 25882 Cov.: 26

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.574

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

GnomAD4 genome AF: 0.555 AC: 83290 AN: 149972 Hom.: 25877 Cov.: 26 AF XY: 0.551 AC XY: 40294 AN XY: 73096

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.700

Gnomad4 NFE AF: 0.708

Gnomad4 OTH AF: 0.569

Alfa AF: 0.628 Hom.: 3961

Bravo AF: 0.539

Asia WGS AF: 0.324 AC: 1127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.6
DANN	Benign	0.49

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: rs28409177; hg19: chr22-36706271;