rs11913874

Positions:

• chr22-36341658-C-G

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.334-132G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0221 in 1,023,528 control chromosomes in the GnomAD database, including 796 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.051 (434 hom., cov: 32)
  • Exomes 𝑓: 0.017 (362 hom.)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0660

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 22-36341658-C-G is Benign according to our data. Variant chr22-36341658-C-G is described in ClinVar as [Benign]. Clinvar id is 1274553.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH9	NM_002473.6	c.334-132G>C		intron_variant		ENST00000216181.11	NP_002464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11	c.334-132G>C		intron_variant		1	NM_002473.6	ENSP00000216181	P1
	ENST00000663925.1	n.87-958C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0510 AC: 7755 AN: 152146 Hom.: 434 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0384

Gnomad ASJ AF: 0.0236

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0161

Gnomad FIN AF: 0.0148

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0134

Gnomad OTH AF: 0.0493

GnomAD4 exome AF: 0.0171 AC: 14856 AN: 871264 Hom.: 362 AF XY: 0.0167 AC XY: 7511 AN XY: 449596

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.0219

Gnomad4 ASJ exome AF: 0.0205

Gnomad4 EAS exome AF: 0.000154

Gnomad4 SAS exome AF: 0.0180

Gnomad4 FIN exome AF: 0.0165

Gnomad4 NFE exome AF: 0.0122

Gnomad4 OTH exome AF: 0.0271

GnomAD4 genome AF: 0.0511 AC: 7777 AN: 152264 Hom.: 434 Cov.: 32 AF XY: 0.0495 AC XY: 3683 AN XY: 74462

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.0384

Gnomad4 ASJ AF: 0.0236

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0157

Gnomad4 FIN AF: 0.0148

Gnomad4 NFE AF: 0.0134

Gnomad4 OTH AF: 0.0493

Alfa AF: 0.0367 Hom.: 41

Bravo AF: 0.0559

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.2
DANN	Benign	0.48

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: rs11913874; hg19: chr22-36737703;