rs2413396

Variant names:

• chr22-36312039-C-T
• rs2413396
• NM_002473.6:c.1728+10G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-36312039-C-T
• chr22-36312039-C-A
• chr22-36312039-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002473.6(MYH9):​c.1728+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 1,613,564 control chromosomes in the GnomAD database, including 646,181 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (49566 hom., cov: 32)
  • Exomes 𝑓: 0.90 (596615 hom.)
• Consequence: MYH9 NM_002473.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: -0.736
• Publications: 26 publications found

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 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 17

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
• May-Hegglin anomaly

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 22-36312039-C-T is Benign according to our data. Variant chr22-36312039-C-T is described in ClinVar as Benign. ClinVar VariationId is 44551.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002473.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH9	NM_002473.6	MANE Select	c.1728+10G>A		intron	N/A	NP_002464.1	P35579-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH9	ENST00000216181.11	TSL:1 MANE Select	c.1728+10G>A		intron	N/A	ENSP00000216181.6	P35579-1
	MYH9	ENST00000685801.1		c.1728+10G>A		intron	N/A	ENSP00000510688.1	A0A8I5KWT8
	MYH9	ENST00000955568.1		c.1728+10G>A		intron	N/A	ENSP00000625627.1

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118812 AN: 151900 Hom.: 49541 Cov.: 32

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.960

Gnomad AMR AF: 0.893

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.909

Gnomad FIN AF: 0.892

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.911

Gnomad OTH AF: 0.829

GnomAD2 exomes AF: 0.880 AC: 221259 AN: 251446 AF XY: 0.888

Gnomad AFR exome AF: 0.433

Gnomad AMR exome AF: 0.937

Gnomad ASJ exome AF: 0.905

Gnomad EAS exome AF: 0.891

Gnomad FIN exome AF: 0.890

Gnomad NFE exome AF: 0.910

Gnomad OTH exome AF: 0.896

GnomAD4 exome AF: 0.900 AC: 1315884 AN: 1461544 Hom.: 596615 Cov.: 54 AF XY: 0.902 AC XY: 655857 AN XY: 727066

African (AFR) AF: 0.427 AC: 14279 AN: 33472

American (AMR) AF: 0.934 AC: 41760 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.899 AC: 23503 AN: 26134

East Asian (EAS) AF: 0.901 AC: 35758 AN: 39698

South Asian (SAS) AF: 0.914 AC: 78806 AN: 86238

European-Finnish (FIN) AF: 0.893 AC: 47682 AN: 53390

Middle Eastern (MID) AF: 0.809 AC: 4529 AN: 5596

European-Non Finnish (NFE) AF: 0.914 AC: 1016190 AN: 1111930

Other (OTH) AF: 0.884 AC: 53377 AN: 60362

GnomAD4 genome AF: 0.782 AC: 118887 AN: 152020 Hom.: 49566 Cov.: 32 AF XY: 0.786 AC XY: 58427 AN XY: 74358

African (AFR) AF: 0.454 AC: 18756 AN: 41342

American (AMR) AF: 0.893 AC: 13675 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.895 AC: 3107 AN: 3470

East Asian (EAS) AF: 0.904 AC: 4671 AN: 5168

South Asian (SAS) AF: 0.910 AC: 4382 AN: 4814

European-Finnish (FIN) AF: 0.892 AC: 9455 AN: 10594

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.911 AC: 61982 AN: 68016

Other (OTH) AF: 0.829 AC: 1745 AN: 2106

Alfa AF: 0.864 Hom.: 87237

Bravo AF: 0.768

Asia WGS AF: 0.855 AC: 2972 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	3	not provided (3)
-	-	2	Autosomal dominant nonsyndromic hearing loss 17 (2)
-	-	1	Atypical hemolytic-uremic syndrome (1)
-	-	1	Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss (1)
-	-	1	MYH9-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.34
DANN	Benign	0.50
PhyloP100		-0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2413396; hg19: chr22-36708084;