rs28482851

Positions:

• chr19-50260629-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001145809.2(MYH14):​c.2355-17C>T variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.164

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 257574.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50260629-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH14	NM_001145809.2	c.2355-17C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000642316.2
MYH14	NM_001077186.2	c.2256-17C>T		splice_polypyrimidine_tract_variant, intron_variant
MYH14	NM_024729.4	c.2232-17C>T		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH14	ENST00000642316.2	c.2355-17C>T		splice_polypyrimidine_tract_variant, intron_variant			NM_001145809.2

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36700 AN: 151600 Hom.: 5174 Cov.: 30

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

GnomAD3 exomes AF: 0.297 AC: 73155 AN: 246226 Hom.: 12166 AF XY: 0.306 AC XY: 40994 AN XY: 133800

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 SAS exome AF: 0.397

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.: 27 AF XY: 0.298 AC XY: 215062 AN XY: 721306

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.172

Gnomad4 ASJ exome AF: 0.377

Gnomad4 EAS exome AF: 0.547

Gnomad4 SAS exome AF: 0.390

Gnomad4 FIN exome AF: 0.277

Gnomad4 NFE exome AF: 0.286

Gnomad4 OTH exome AF: 0.293

GnomAD4 genome AF: 0.242 AC: 36701 AN: 151718 Hom.: 5175 Cov.: 30 AF XY: 0.243 AC XY: 17969 AN XY: 74098

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.235

Alfa AF: 0.284 Hom.: 1706

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

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 24, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Autosomal dominant nonsyndromic hearing loss 4A Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.85
DANN	Benign	0.78

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

Other links and lift over

dbSNP: rs28482851; hg19: chr19-50763886; COSMIC: COSV51828964; COSMIC: COSV51828964;