NM_001145809.2:c.2680C>A

Variant names:

• chr19-50263406-C-A
• rs34805056
• NM_001145809.2:c.2680C>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001145809.2(MYH14):​c.2680C>A​(p.Arg894Arg) 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
• Publications: 2 publications found

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]

MYH14 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 4A

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 93 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145809.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH14	NM_001145809.2	MANE Select	c.2680C>A	p.Arg894Arg	synonymous	Exon 22 of 43	NP_001139281.1	Q7Z406-2
	MYH14	NM_001077186.2		c.2581C>A	p.Arg861Arg	synonymous	Exon 21 of 42	NP_001070654.1	Q7Z406-6
	MYH14	NM_024729.4		c.2557C>A	p.Arg853Arg	synonymous	Exon 20 of 41	NP_079005.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH14	ENST00000642316.2	MANE Select	c.2680C>A	p.Arg894Arg	synonymous	Exon 22 of 43	ENSP00000493594.1	Q7Z406-2
	MYH14	ENST00000599920.5	TSL:1	c.2581C>A	p.Arg861Arg	synonymous	Exon 21 of 24	ENSP00000469573.1	M0QY43
	MYH14	ENST00000425460.6	TSL:5	c.2581C>A	p.Arg861Arg	synonymous	Exon 21 of 42	ENSP00000407879.1	Q7Z406-6

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

GnomAD2 exomes AF: 0.000183 AC: 41 AN: 224406 AF XY: 0.000156

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 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

African (AFR) AF: 0.00203 AC: 67 AN: 33076

American (AMR) AF: 0.000234 AC: 10 AN: 42782

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25884

East Asian (EAS) AF: 0.00 AC: 0 AN: 39038

South Asian (SAS) AF: 0.00 AC: 0 AN: 84012

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52096

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5690

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1105968

Other (OTH) AF: 0.000184 AC: 11 AN: 59838

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

African (AFR) AF: 0.00212 AC: 88 AN: 41542

American (AMR) AF: 0.000196 AC: 3 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68014

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000139 Hom.: 0

Bravo AF: 0.000688

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	11
DANN	Benign	0.63
PhyloP100		0.87
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs34805056; hg19: chr19-50766663;