19-50210294-G-A

Position:

• chr19-50210294-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001145809.2(MYH14):​c.-3-69G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0096 in 1,399,822 control chromosomes in the GnomAD database, including 134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (42 hom., cov: 32)
  • Exomes 𝑓: 0.0085 (92 hom.)
• Consequence: MYH14 NM_001145809.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.83

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=-0.85).
• BP6: Variant 19-50210294-G-A is Benign according to our data. Variant chr19-50210294-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1182737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0188 (2863/152210) while in subpopulation AFR AF= 0.0419 (1741/41540). AF 95% confidence interval is 0.0403. There are 42 homozygotes in gnomad4. There are 1402 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2863 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH14	NM_001145809.2	c.-3-69G>A		intron_variant		ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2	c.-3-69G>A		intron_variant			NP_001070654.1
MYH14	NM_024729.4	c.-3-69G>A		intron_variant			NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2	c.-3-69G>A		intron_variant			NM_001145809.2	ENSP00000493594

Frequencies

GnomAD3 genomes AF: 0.0188 AC: 2858 AN: 152094 Hom.: 42 Cov.: 32

Gnomad AFR AF: 0.0419

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0194

Gnomad ASJ AF: 0.0219

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0143

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00779

Gnomad OTH AF: 0.0244

GnomAD4 exome AF: 0.00847 AC: 10573 AN: 1247612 Hom.: 92 AF XY: 0.00812 AC XY: 4979 AN XY: 613464

Gnomad4 AFR exome AF: 0.0432

Gnomad4 AMR exome AF: 0.0103

Gnomad4 ASJ exome AF: 0.0232

Gnomad4 EAS exome AF: 0.0000328

Gnomad4 SAS exome AF: 0.000601

Gnomad4 FIN exome AF: 0.0120

Gnomad4 NFE exome AF: 0.00766

Gnomad4 OTH exome AF: 0.0121

GnomAD4 genome AF: 0.0188 AC: 2863 AN: 152210 Hom.: 42 Cov.: 32 AF XY: 0.0188 AC XY: 1402 AN XY: 74420

Gnomad4 AFR AF: 0.0419

Gnomad4 AMR AF: 0.0194

Gnomad4 ASJ AF: 0.0219

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.0143

Gnomad4 NFE AF: 0.00779

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.0141 Hom.: 5

Bravo AF: 0.0208

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.4
DANN	Benign	0.77

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: rs116165622; hg19: chr19-50713551;