NM_001145809.2:c.2355-17C>T

Variant names:

• chr19-50260629-C-T
• rs28482851
• NM_001145809.2:c.2355-17C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001145809.2(MYH14):​c.2355-17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,600,346 control chromosomes in the GnomAD database, including 71,435 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (5175 hom., cov: 30)
  • Exomes 𝑓: 0.29 (66260 hom.)
• Consequence: MYH14 NM_001145809.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.164
• Publications: 9 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 19-50260629-C-T is Benign according to our data. Variant chr19-50260629-C-T is described in ClinVar as Benign. ClinVar VariationId is 257574.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

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.2355-17C>T		intron	N/A	NP_001139281.1	Q7Z406-2
	MYH14	NM_001077186.2		c.2256-17C>T		intron	N/A	NP_001070654.1	Q7Z406-6
	MYH14	NM_024729.4		c.2232-17C>T		intron	N/A	NP_079005.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH14	ENST00000642316.2	MANE Select	c.2355-17C>T		intron	N/A	ENSP00000493594.1	Q7Z406-2
	MYH14	ENST00000599920.5	TSL:1	c.2256-17C>T		intron	N/A	ENSP00000469573.1	M0QY43
	MYH14	ENST00000425460.6	TSL:5	c.2256-17C>T		intron	N/A	ENSP00000407879.1	Q7Z406-6

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36700 AN: 151600 Hom.: 5174 Cov.: 30

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.226

GnomAD2 exomes AF: 0.297 AC: 73155 AN: 246226 AF XY: 0.306

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.171

Gnomad ASJ exome AF: 0.378

Gnomad EAS exome AF: 0.539

Gnomad FIN exome AF: 0.278

Gnomad NFE exome AF: 0.291

Gnomad OTH exome AF: 0.282

GnomAD4 exome AF: 0.294 AC: 426034 AN: 1448628 Hom.: 66260 Cov.: 27 AF XY: 0.298 AC XY: 215062 AN XY: 721306

African (AFR) AF: 0.116 AC: 3857 AN: 33250

American (AMR) AF: 0.172 AC: 7652 AN: 44424

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 9804 AN: 26012

East Asian (EAS) AF: 0.547 AC: 21621 AN: 39534

South Asian (SAS) AF: 0.390 AC: 33466 AN: 85800

European-Finnish (FIN) AF: 0.277 AC: 14734 AN: 53154

Middle Eastern (MID) AF: 0.358 AC: 2057 AN: 5746

European-Non Finnish (NFE) AF: 0.286 AC: 315291 AN: 1100790

Other (OTH) AF: 0.293 AC: 17552 AN: 59918

GnomAD4 genome AF: 0.242 AC: 36701 AN: 151718 Hom.: 5175 Cov.: 30 AF XY: 0.243 AC XY: 17969 AN XY: 74098

African (AFR) AF: 0.120 AC: 4968 AN: 41376

American (AMR) AF: 0.174 AC: 2656 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1331 AN: 3464

East Asian (EAS) AF: 0.528 AC: 2703 AN: 5124

South Asian (SAS) AF: 0.393 AC: 1882 AN: 4784

European-Finnish (FIN) AF: 0.272 AC: 2865 AN: 10542

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19468 AN: 67880

Other (OTH) AF: 0.235 AC: 494 AN: 2106

Alfa AF: 0.252 Hom.: 3750

Bravo AF: 0.231

Asia WGS AF: 0.403 AC: 1404 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	1	Autosomal dominant nonsyndromic hearing loss 4A (1)
-	-	1	Peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.85
DANN	Benign	0.78
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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: rs28482851; hg19: chr19-50763886; COSMIC: COSV51828964; COSMIC: COSV51828964;