Variant rs2056841 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016239.4(MYO15A):c.7655-17G>A variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.01

Variant links:

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 links:

LOC124903944 (HGNC:):

LOC124903944 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 260702.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-18151378-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
MYO15A	NM_016239.4 linkuse as main transcript	c.7655-17G>A	splice_polypyrimidine_tract_variant, intron_variant	ENST00000647165.2	NP_057323.3
LOC124903944	XR_007065652.1 linkuse as main transcript	n.377+225C>T	intron_variant, non_coding_transcript_variant
MYO15A	XM_017024714.3 linkuse as main transcript	c.7595-17G>A	splice_polypyrimidine_tract_variant, intron_variant		XP_016880203.1
MYO15A	XM_017024715.3 linkuse as main transcript	c.7658-17G>A	splice_polypyrimidine_tract_variant, intron_variant		XP_016880204.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO15A	ENST00000647165.2 linkuse as main transcript	c.7655-17G>A		splice_polypyrimidine_tract_variant, intron_variant			NM_016239.4	ENSP00000495481	P1	Q9UKN7-1

Frequencies

GnomAD3 genomes

AF:

0.160

AC:

24355

AN:

152034

Hom.:

2520

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.188

AC:

46912

AN:

249418

Hom.:

6489

AF XY:

0.177

AC XY:

23907

AN XY:

135356

show subpopulations

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 SAS exome

AF:

0.152

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.:

AF XY:

0.142

AC XY:

103233

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.144

Gnomad4 AMR exome

AF:

0.347

Gnomad4 ASJ exome

AF:

0.125

Gnomad4 EAS exome

AF:

0.494

Gnomad4 SAS exome

AF:

0.154

Gnomad4 FIN exome

AF:

0.173

Gnomad4 NFE exome

AF:

0.119

Gnomad4 OTH exome

AF:

0.160

GnomAD4 genome

AF:

0.160

AC:

24369

AN:

152152

Hom.:

2527

Cov.:

AF XY:

0.169

AC XY:

12545

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.148

Gnomad4 AMR

AF:

0.265

Gnomad4 ASJ

AF:

0.119

Gnomad4 EAS

AF:

0.510

Gnomad4 SAS

AF:

0.162

Gnomad4 FIN

AF:

0.180

Gnomad4 NFE

AF:

0.118

Gnomad4 OTH

AF:

0.157

Alfa

AF:

0.140

Hom.:

328

Bravo

AF:

0.169

Asia WGS

AF:

0.298

AC:

1038

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.34

DANN

Benign

0.57

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over