rs1557538

chr22-36316918-A-Gchr22-36316918-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002473.6(MYH9):c.1228-249T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 143,450 control chromosomes in the GnomAD database, including 24,735 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.56 (24735 hom., cov: 31)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0380

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 22-36316918-A-G is Benign according to our data. Variant chr22-36316918-A-G is described in ClinVar as [Benign]. Clinvar id is 1181576.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH9	NM_002473.6	c.1228-249T>C		intron_variant		ENST00000216181.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH9	ENST00000216181.11	c.1228-249T>C		intron_variant		1	NM_002473.6	P1

Frequencies

GnomAD3 genomes AF: 0.563 AC: 80635 AN: 143340 Hom.: 24729 Cov.: 31

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.629

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.530

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.562 AC: 80661 AN: 143450 Hom.: 24735 Cov.: 31 AF XY: 0.556 AC XY: 39056 AN XY: 70194

Gnomad4 AFR AF: 0.361

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.654

Gnomad4 NFE AF: 0.690

Gnomad4 OTH AF: 0.583

Alfa AF: 0.618 Hom.: 4583

Bravo AF: 0.564

Asia WGS AF: 0.245 AC: 819 AN: 3348

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	2.1
Dann	Benign	0.65

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: rs1557538; hg19: chr22-36712963;