rs7078

Variant names:

• chr22-36281868-A-G
• rs7078
• NM_002473.6:c.*800T>C

Your query was ambiguous. Multiple possible variants found:

• chr22-36281868-A-G
• chr22-36281868-A-C

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_002473.6(MYH9):​c.*800T>C variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.241 in 230,108 control chromosomes in the GnomAD database, including 7,389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4507 hom., cov: 33)
  • Exomes 𝑓: 0.26 (2882 hom.)
• Consequence: MYH9 NM_002473.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 5.41
• Publications: 25 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: G2P, Labcorp Genetics (formerly Invitae)
• macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 22-36281868-A-G is Benign according to our data. Variant chr22-36281868-A-G is described in ClinVar as Benign. ClinVar VariationId is 341469.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.291 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.*800T>C		3_prime_UTR	Exon 41 of 41	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.*800T>C		3_prime_UTR	Exon 41 of 41	ENSP00000216181.6	P35579-1
	MYH9	ENST00000685801.1		c.*800T>C		3_prime_UTR	Exon 42 of 42	ENSP00000510688.1	A0A8I5KWT8
	MYH9	ENST00000955568.1		c.*800T>C		3_prime_UTR	Exon 42 of 42	ENSP00000625627.1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35476 AN: 152104 Hom.: 4504 Cov.: 33

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.0749

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.257 AC: 19978 AN: 77886 Hom.: 2882 Cov.: 0 AF XY: 0.258 AC XY: 9254 AN XY: 35910

African (AFR) AF: 0.149 AC: 546 AN: 3666

American (AMR) AF: 0.232 AC: 555 AN: 2396

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1602 AN: 4888

East Asian (EAS) AF: 0.0712 AC: 783 AN: 10998

South Asian (SAS) AF: 0.191 AC: 129 AN: 674

European-Finnish (FIN) AF: 0.246 AC: 118 AN: 480

Middle Eastern (MID) AF: 0.303 AC: 141 AN: 466

European-Non Finnish (NFE) AF: 0.300 AC: 14341 AN: 47842

Other (OTH) AF: 0.272 AC: 1763 AN: 6476

GnomAD4 genome AF: 0.233 AC: 35487 AN: 152222 Hom.: 4507 Cov.: 33 AF XY: 0.229 AC XY: 17034 AN XY: 74432

African (AFR) AF: 0.146 AC: 6081 AN: 41548

American (AMR) AF: 0.229 AC: 3500 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1129 AN: 3470

East Asian (EAS) AF: 0.0747 AC: 388 AN: 5192

South Asian (SAS) AF: 0.195 AC: 942 AN: 4828

European-Finnish (FIN) AF: 0.252 AC: 2671 AN: 10602

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20029 AN: 67966

Other (OTH) AF: 0.228 AC: 482 AN: 2114

Alfa AF: 0.257 Hom.: 2445

Bravo AF: 0.231

Asia WGS AF: 0.118 AC: 413 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Autosomal dominant nonsyndromic hearing loss 17 (1)
-	-	1	MYH9-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Benign	0.88
PhyloP100		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7078;

hg19: chr22-36677914;

COSMIC: COSV53385097;

COSMIC: COSV53385097;