rs28482851

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001145809.2(MYH14):c.2355-17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,600,346 control chromosomes in the GnomAD database, including 71,435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 5175 hom., cov: 30)

Exomes 𝑓: 0.29 ( 66260 hom. )

Consequence

MYH14
NM_001145809.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.164

Publications

9 publications found

Variant links:

Genes affected

MYH14 (HGNC:23212): (myosin heavy chain 14) This gene encodes a member of the myosin superfamily. The protein represents a conventional non-muscle myosin; it should not be confused with the unconventional myosin-14 (MYO14). Myosins are actin-dependent motor proteins with diverse functions including regulation of cytokinesis, cell motility, and cell polarity. Mutations in this gene result in one form of autosomal dominant hearing impairment. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

MYH14 Gene-Disease associations (from GenCC):

autosomal dominant nonsyndromic hearing loss 4A
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
nonsyndromic genetic hearing loss
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

MYH14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 19-50260629-C-T is Benign according to our data. Variant chr19-50260629-C-T is described in ClinVar as Benign. ClinVar VariationId is 257574.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MYH14	NM_001145809.2 link	c.2355-17C>T	intron_variant	Intron 19 of 42	ENST00000642316.2	NP_001139281.1	Q7Z406-2A1L2Z2B3KWH4
MYH14	NM_001077186.2 link	c.2256-17C>T	intron_variant	Intron 18 of 41		NP_001070654.1	Q7Z406-6B3KWH4
MYH14	NM_024729.4 link	c.2232-17C>T	intron_variant	Intron 17 of 40		NP_079005.3	Q7Z406-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2 link	c.2355-17C>T		intron_variant	Intron 19 of 42		NM_001145809.2	ENSP00000493594.1		Q7Z406-2

Frequencies

GnomAD3 genomes

AF:

0.242

AC:

36700

AN:

151600

Hom.:

5174

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.260

Gnomad AMR

AF:

0.175

Gnomad ASJ

AF:

0.384

Gnomad EAS

AF:

0.529

Gnomad SAS

AF:

0.395

Gnomad FIN

AF:

0.272

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.287

Gnomad OTH

AF:

0.226

GnomAD2 exomes

AF:

0.297

AC:

73155

AN:

246226

AF XY:

0.306

show subpopulations

Gnomad AFR exome

AF:

0.119

Gnomad AMR exome

AF:

0.171

Gnomad ASJ exome

AF:

0.378

Gnomad EAS exome

AF:

0.539

Gnomad FIN exome

AF:

0.278

Gnomad NFE exome

AF:

0.291

Gnomad OTH exome

AF:

0.282

GnomAD4 exome

AF:

0.294

AC:

426034

AN:

1448628

Hom.:

66260

Cov.:

AF XY:

0.298

AC XY:

215062

AN XY:

721306

show subpopulations

African (AFR)

AF:

0.116

AC:

3857

AN:

33250

American (AMR)

AF:

0.172

AC:

7652

AN:

44424

Ashkenazi Jewish (ASJ)

AF:

0.377

AC:

9804

AN:

26012

East Asian (EAS)

AF:

0.547

AC:

21621

AN:

39534

South Asian (SAS)

AF:

0.390

AC:

33466

AN:

85800

European-Finnish (FIN)

AF:

0.277

AC:

14734

AN:

53154

Middle Eastern (MID)

AF:

0.358

AC:

2057

AN:

5746

European-Non Finnish (NFE)

AF:

0.286

AC:

315291

AN:

1100790

Other (OTH)

AF:

0.293

AC:

17552

AN:

59918

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

13444

26887

40331

53774

67218

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10492

20984

31476

41968

52460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.242

AC:

36701

AN:

151718

Hom.:

5175

Cov.:

AF XY:

0.243

AC XY:

17969

AN XY:

74098

show subpopulations

African (AFR)

AF:

0.120

AC:

4968

AN:

41376

American (AMR)

AF:

0.174

AC:

2656

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.384

AC:

1331

AN:

3464

East Asian (EAS)

AF:

0.528

AC:

2703

AN:

5124

South Asian (SAS)

AF:

0.393

AC:

1882

AN:

4784

European-Finnish (FIN)

AF:

0.272

AC:

2865

AN:

10542

Middle Eastern (MID)

AF:

0.333

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.287

AC:

19468

AN:

67880

Other (OTH)

AF:

0.235

AC:

494

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1315

2630

3945

5260

6575

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.252

Hom.:

3750

Bravo

AF:

0.231

Asia WGS

AF:

0.403

AC:

1404

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 24, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal dominant nonsyndromic hearing loss 4A

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.85

(source)

DANN

Benign

0.78

PhyloP100

0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over