19-50263406-C-A

Position:

• chr19-50263406-C-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001145809.2(MYH14):​c.2680C>A​(p.Arg894=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 1,600,596 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00061 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000064 (1 hom.)
• Consequence: MYH14 NM_001145809.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.869

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP6: Variant 19-50263406-C-A is Benign according to our data. Variant chr19-50263406-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 517425.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.869 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000611 (93/152212) while in subpopulation AFR AF= 0.00212 (88/41542). AF 95% confidence interval is 0.00176. There are 0 homozygotes in gnomad4. There are 45 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 93 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH14	NM_001145809.2	c.2680C>A	p.Arg894=	synonymous_variant	22/43	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2	c.2581C>A	p.Arg861=	synonymous_variant	21/42		NP_001070654.1
MYH14	NM_024729.4	c.2557C>A	p.Arg853=	synonymous_variant	20/41		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2	c.2680C>A	p.Arg894=	synonymous_variant	22/43		NM_001145809.2	ENSP00000493594

Frequencies

GnomAD3 genomes AF: 0.000611 AC: 93 AN: 152094 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00212

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000183 AC: 41 AN: 224406 Hom.: 1 AF XY: 0.000156 AC XY: 19 AN XY: 121920

Gnomad AFR exome AF: 0.00280

Gnomad AMR exome AF: 0.0000943

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000999

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000635 AC: 92 AN: 1448384 Hom.: 1 Cov.: 30 AF XY: 0.0000500 AC XY: 36 AN XY: 719362

Gnomad4 AFR exome AF: 0.00203

Gnomad4 AMR exome AF: 0.000234

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000271

Gnomad4 OTH exome AF: 0.000184

GnomAD4 genome AF: 0.000611 AC: 93 AN: 152212 Hom.: 0 Cov.: 32 AF XY: 0.000605 AC XY: 45 AN XY: 74424

Gnomad4 AFR AF: 0.00212

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000139 Hom.: 0

Bravo AF: 0.000688

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 17, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 28, 2023	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 10, 2017

p.Arg894Arg in exon 22 of MYH14: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 0.23% (50/21448) of African chromosomes including 1 homozygote by the Genome Aggregation Databas e (gnomAD, http://gnomad.broadinstitute.org/; dbSNP rs34805056). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	11
DANN	Benign	0.63

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: rs34805056; hg19: chr19-50766663;