chr19-50217817-G-A

Position:

• chr19-50217817-G-A

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.562+46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 1,597,016 control chromosomes in the GnomAD database, including 78,002 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5147 hom., cov: 31)
  • Exomes 𝑓: 0.31 (72855 hom.)
• Consequence: MYH14 NM_001145809.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.420

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=-0.86).
• BP6: Variant 19-50217817-G-A is Benign according to our data. Variant chr19-50217817-G-A is described in ClinVar as [Benign]. Clinvar id is 1295265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH14	NM_001145809.2	c.562+46G>A		intron_variant		ENST00000642316.2
MYH14	NM_001077186.2	c.562+46G>A		intron_variant
MYH14	NM_024729.4	c.562+46G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH14	ENST00000642316.2	c.562+46G>A		intron_variant			NM_001145809.2

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37443 AN: 151944 Hom.: 5142 Cov.: 31

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.254

GnomAD3 exomes AF: 0.282 AC: 66054 AN: 234006 Hom.: 9990 AF XY: 0.294 AC XY: 37716 AN XY: 128092

Gnomad AFR exome AF: 0.110

Gnomad AMR exome AF: 0.193

Gnomad ASJ exome AF: 0.288

Gnomad EAS exome AF: 0.241

Gnomad SAS exome AF: 0.387

Gnomad FIN exome AF: 0.274

Gnomad NFE exome AF: 0.312

Gnomad OTH exome AF: 0.288

GnomAD4 exome AF: 0.313 AC: 451823 AN: 1444954 Hom.: 72855 Cov.: 33 AF XY: 0.316 AC XY: 226460 AN XY: 717672

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.196

Gnomad4 ASJ exome AF: 0.283

Gnomad4 EAS exome AF: 0.273

Gnomad4 SAS exome AF: 0.383

Gnomad4 FIN exome AF: 0.272

Gnomad4 NFE exome AF: 0.322

Gnomad4 OTH exome AF: 0.303

GnomAD4 genome AF: 0.246 AC: 37449 AN: 152062 Hom.: 5147 Cov.: 31 AF XY: 0.245 AC XY: 18175 AN XY: 74320

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.297

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.315

Gnomad4 OTH AF: 0.256

Alfa AF: 0.297 Hom.: 12144

Bravo AF: 0.235

Asia WGS AF: 0.317 AC: 1100 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.69

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: rs4802666; hg19: chr19-50721074;