rs2056841

Variant names:

• chr17-18151378-G-A
• rs2056841
• NM_016239.4:c.7655-17G>A

Variant summary

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

The NM_016239.4(MYO15A):​c.7655-17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,613,996 control chromosomes in the GnomAD database, including 21,864 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2527 hom., cov: 32)
  • Exomes 𝑓: 0.14 (19337 hom.)
• Consequence: MYO15A NM_016239.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.01
• Publications: 10 publications found

Genes affected

MYO15A (HGNC:7594): (myosin XVA) This gene encodes an unconventional myosin. This protein differs from other myosins in that it has a long N-terminal extension preceding the conserved motor domain. Studies in mice suggest that this protein is necessary for actin organization in the hair cells of the cochlea. Mutations in this gene have been associated with profound, congenital, neurosensory, nonsyndromal deafness. This gene is located within the Smith-Magenis syndrome region on chromosome 17. Read-through transcripts containing an upstream gene and this gene have been identified, but they are not thought to encode a fusion protein. Several alternatively spliced transcript variants have been described, but their full length sequences have not been determined. [provided by RefSeq, Jul 2008]

MYO15A Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LOC124903944 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-18151378-G-A is Benign according to our data. Variant chr17-18151378-G-A is described in ClinVar as Benign. ClinVar VariationId is 260702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016239.4. 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
	MYO15A	NM_016239.4	MANE Select	c.7655-17G>A		intron	N/A	NP_057323.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO15A	ENST00000647165.2	MANE Select	c.7655-17G>A		intron	N/A	ENSP00000495481.1	Q9UKN7-1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24355 AN: 152034 Hom.: 2520 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.155

GnomAD2 exomes AF: 0.188 AC: 46912 AN: 249418 AF XY: 0.177

Gnomad AFR exome AF: 0.150

Gnomad AMR exome AF: 0.361

Gnomad ASJ exome AF: 0.122

Gnomad EAS exome AF: 0.508

Gnomad FIN exome AF: 0.171

Gnomad NFE exome AF: 0.110

Gnomad OTH exome AF: 0.157

GnomAD4 exome AF: 0.143 AC: 208695 AN: 1461844 Hom.: 19337 Cov.: 37 AF XY: 0.142 AC XY: 103233 AN XY: 727228

African (AFR) AF: 0.144 AC: 4828 AN: 33478

American (AMR) AF: 0.347 AC: 15528 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 3257 AN: 26136

East Asian (EAS) AF: 0.494 AC: 19629 AN: 39700

South Asian (SAS) AF: 0.154 AC: 13261 AN: 86258

European-Finnish (FIN) AF: 0.173 AC: 9251 AN: 53404

Middle Eastern (MID) AF: 0.0856 AC: 494 AN: 5768

European-Non Finnish (NFE) AF: 0.119 AC: 132806 AN: 1111996

Other (OTH) AF: 0.160 AC: 9641 AN: 60394

GnomAD4 genome AF: 0.160 AC: 24369 AN: 152152 Hom.: 2527 Cov.: 32 AF XY: 0.169 AC XY: 12545 AN XY: 74368

African (AFR) AF: 0.148 AC: 6140 AN: 41514

American (AMR) AF: 0.265 AC: 4048 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 414 AN: 3472

East Asian (EAS) AF: 0.510 AC: 2634 AN: 5162

South Asian (SAS) AF: 0.162 AC: 780 AN: 4816

European-Finnish (FIN) AF: 0.180 AC: 1912 AN: 10600

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8012 AN: 67980

Other (OTH) AF: 0.157 AC: 332 AN: 2110

Alfa AF: 0.140 Hom.: 339

Bravo AF: 0.169

Asia WGS AF: 0.298 AC: 1038 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.34
DANN	Benign	0.57
PhyloP100		-1.0
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: rs2056841; hg19: chr17-18054692; COSMIC: COSV52753511; COSMIC: COSV52753511;