19-50257459-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001145809.2(MYH14):​c.2205C>G​(p.Arg735Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 1,602,566 control chromosomes in the GnomAD database, including 143,410 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11520 hom., cov: 32)
Exomes 𝑓: 0.42 ( 131890 hom. )

Consequence

MYH14
NM_001145809.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 3.21

Publications

19 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP6
Variant 19-50257459-C-G is Benign according to our data. Variant chr19-50257459-C-G is described in ClinVar as Benign. ClinVar VariationId is 44055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=3.21 with no splicing effect.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145809.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
MYH14
NM_001145809.2
MANE Select
c.2205C>Gp.Arg735Arg
synonymous
Exon 18 of 43NP_001139281.1
MYH14
NM_001077186.2
c.2106C>Gp.Arg702Arg
synonymous
Exon 17 of 42NP_001070654.1
MYH14
NM_024729.4
c.2082C>Gp.Arg694Arg
synonymous
Exon 16 of 41NP_079005.3

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
MYH14
ENST00000642316.2
MANE Select
c.2205C>Gp.Arg735Arg
synonymous
Exon 18 of 43ENSP00000493594.1
MYH14
ENST00000599920.5
TSL:1
c.2106C>Gp.Arg702Arg
synonymous
Exon 17 of 24ENSP00000469573.1
MYH14
ENST00000425460.6
TSL:5
c.2106C>Gp.Arg702Arg
synonymous
Exon 17 of 42ENSP00000407879.1

Frequencies

GnomAD3 genomes
AF:
0.383
AC:
58212
AN:
151958
Hom.:
11525
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.317
Gnomad AMI
AF:
0.353
Gnomad AMR
AF:
0.313
Gnomad ASJ
AF:
0.479
Gnomad EAS
AF:
0.383
Gnomad SAS
AF:
0.374
Gnomad FIN
AF:
0.364
Gnomad MID
AF:
0.455
Gnomad NFE
AF:
0.437
Gnomad OTH
AF:
0.408
GnomAD2 exomes
AF:
0.382
AC:
88552
AN:
231796
AF XY:
0.390
show subpopulations
Gnomad AFR exome
AF:
0.299
Gnomad AMR exome
AF:
0.247
Gnomad ASJ exome
AF:
0.486
Gnomad EAS exome
AF:
0.387
Gnomad FIN exome
AF:
0.360
Gnomad NFE exome
AF:
0.430
Gnomad OTH exome
AF:
0.410
GnomAD4 exome
AF:
0.424
AC:
614762
AN:
1450490
Hom.:
131890
Cov.:
50
AF XY:
0.424
AC XY:
305183
AN XY:
720294
show subpopulations
African (AFR)
AF:
0.312
AC:
10389
AN:
33290
American (AMR)
AF:
0.261
AC:
11299
AN:
43276
Ashkenazi Jewish (ASJ)
AF:
0.482
AC:
12444
AN:
25828
East Asian (EAS)
AF:
0.349
AC:
13716
AN:
39346
South Asian (SAS)
AF:
0.387
AC:
32639
AN:
84342
European-Finnish (FIN)
AF:
0.368
AC:
19405
AN:
52686
Middle Eastern (MID)
AF:
0.497
AC:
2860
AN:
5754
European-Non Finnish (NFE)
AF:
0.440
AC:
486965
AN:
1105942
Other (OTH)
AF:
0.417
AC:
25045
AN:
60026
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.465
Heterozygous variant carriers
0
18981
37962
56943
75924
94905
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
14726
29452
44178
58904
73630
<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:
0.383
AC:
58220
AN:
152076
Hom.:
11520
Cov.:
32
AF XY:
0.378
AC XY:
28091
AN XY:
74340
show subpopulations
African (AFR)
AF:
0.317
AC:
13149
AN:
41504
American (AMR)
AF:
0.313
AC:
4770
AN:
15262
Ashkenazi Jewish (ASJ)
AF:
0.479
AC:
1663
AN:
3472
East Asian (EAS)
AF:
0.383
AC:
1975
AN:
5156
South Asian (SAS)
AF:
0.373
AC:
1797
AN:
4824
European-Finnish (FIN)
AF:
0.364
AC:
3847
AN:
10582
Middle Eastern (MID)
AF:
0.445
AC:
130
AN:
292
European-Non Finnish (NFE)
AF:
0.437
AC:
29702
AN:
67958
Other (OTH)
AF:
0.409
AC:
865
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1839
3677
5516
7354
9193
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
564
1128
1692
2256
2820
<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:
0.428
Hom.:
4659
Bravo
AF:
0.379
Asia WGS
AF:
0.335
AC:
1169
AN:
3478

ClinVar

ClinVar submissions as Germline

Significance:Benign
Revision:criteria provided, multiple submitters, no conflicts
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
-
5
not specified (5)
-
-
2
Autosomal dominant nonsyndromic hearing loss 4A (2)
-
-
2
not provided (2)
-
-
1
Peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.28
CADD
Benign
11
DANN
Benign
0.82
PhyloP100
3.2
Mutation Taster
=57/43
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

Publications

Other links and lift over

dbSNP: rs378811; hg19: chr19-50760716; COSMIC: COSV51816085; COSMIC: COSV51816085; API