chr19-50255315-G-A

Position:

• chr19-50255315-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145809.2(MYH14):​c.2041G>A​(p.Gly681Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,398,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Benignin Lovd.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MYH14 NM_001145809.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2056252).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH14	NM_001145809.2	c.2041G>A	p.Gly681Arg	missense_variant	17/43	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2	c.1946-1984G>A		intron_variant			NP_001070654.1
MYH14	NM_024729.4	c.1922-1984G>A		intron_variant			NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2	c.2041G>A	p.Gly681Arg	missense_variant	17/43		NM_001145809.2	ENSP00000493594

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000130 AC: 2 AN: 153548 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 81522

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000405

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000917

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1398014 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 689628

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000280

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Benign	0.95
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.40
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.55	.;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.58	T
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Pathogenic	0.79	T
Sift4G	Uncertain	0.0060	.;D
Polyphen		0.0030	B;B
Vest4		0.21
MutPred		0.36		Gain of solvent accessibility (P = 0.0097);Gain of solvent accessibility (P = 0.0097);
MVP		0.068
MPC		1.2
ClinPred		0.15	T
GERP RS		3.2
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs75915336; hg19: chr19-50758572;