Variant chr22-36305891-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002473.6(MYH9):c.2159+39C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0424 in 1,611,282 control chromosomes in the GnomAD database, including 1,682 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 117 hom., cov: 33)

Exomes 𝑓: 0.043 ( 1565 hom. )

Consequence

MYH9
NM_002473.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.65

Variant links:

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]

MYH9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 22-36305891-G-T is Benign according to our data. Variant chr22-36305891-G-T is described in ClinVar as [Benign]. Clinvar id is 258733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0328 (5002/152296) while in subpopulation NFE AF= 0.0493 (3356/68008). AF 95% confidence interval is 0.048. There are 117 homozygotes in gnomad4. There are 2344 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 5002 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH9	NM_002473.6 linkuse as main transcript	c.2159+39C>A		intron_variant		ENST00000216181.11	NP_002464.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH9	ENST00000216181.11 linkuse as main transcript	c.2159+39C>A	intron_variant		1	NM_002473.6	ENSP00000216181	P1	P35579-1
MYH9	ENST00000685801.1 linkuse as main transcript	c.2222+39C>A	intron_variant				ENSP00000510688
MYH9	ENST00000687922.1 linkuse as main transcript	n.534C>A	non_coding_transcript_exon_variant	3/3
MYH9	ENST00000691109.1 linkuse as main transcript	n.2454+39C>A	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0329

AC:

5000

AN:

152178

Hom.:

117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0102

Gnomad AMI

AF:

0.0637

Gnomad AMR

AF:

0.0405

Gnomad ASJ

AF:

0.0530

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00746

Gnomad FIN

AF:

0.0228

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0493

Gnomad OTH

AF:

0.0339

GnomAD3 exomes

AF:

0.0345

AC:

8589

AN:

249288

Hom.:

202

AF XY:

0.0350

AC XY:

4740

AN XY:

135364

show subpopulations

Gnomad AFR exome

AF:

0.00938

Gnomad AMR exome

AF:

0.0289

Gnomad ASJ exome

AF:

0.0582

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00915

Gnomad FIN exome

AF:

0.0231

Gnomad NFE exome

AF:

0.0517

Gnomad OTH exome

AF:

0.0454

GnomAD4 exome

AF:

0.0434

AC:

63309

AN:

1458986

Hom.:

1565

Cov.:

AF XY:

0.0426

AC XY:

30908

AN XY:

725762

show subpopulations

Gnomad4 AFR exome

AF:

0.00760

Gnomad4 AMR exome

AF:

0.0300

Gnomad4 ASJ exome

AF:

0.0583

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00886

Gnomad4 FIN exome

AF:

0.0244

Gnomad4 NFE exome

AF:

0.0498

Gnomad4 OTH exome

AF:

0.0425

GnomAD4 genome

AF:

0.0328

AC:

5002

AN:

152296

Hom.:

117

Cov.:

AF XY:

0.0315

AC XY:

2344

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0101

Gnomad4 AMR

AF:

0.0405

Gnomad4 ASJ

AF:

0.0530

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00767

Gnomad4 FIN

AF:

0.0228

Gnomad4 NFE

AF:

0.0493

Gnomad4 OTH

AF:

0.0336

Alfa

AF:

0.0202

Hom.:

Bravo

AF:

0.0347

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Jun 29, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.4

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over