17-10392304-CA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002472.3(MYH8):c.5568+237del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,154 control chromosomes in the GnomAD database, including 2,330 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (2330 hom., cov: 30)
• Consequence: MYH8 NM_002472.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.614

Genes affected

MYH8 (HGNC:7578): (myosin heavy chain 8) Myosins are actin-based motor proteins that function in the generation of mechanical force in eukaryotic cells. Muscle myosins are heterohexamers composed of 2 myosin heavy chains and 2 pairs of nonidentical myosin light chains. This gene encodes a member of the class II or conventional myosin heavy chains, and functions in skeletal muscle contraction. This gene is predominantly expressed in fetal skeletal muscle. This gene is found in a cluster of myosin heavy chain genes on chromosome 17. A mutation in this gene results in trismus-pseudocamptodactyly syndrome. [provided by RefSeq, Sep 2009]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 17-10392304-CA-C is Benign according to our data. Variant chr17-10392304-CA-C is described in ClinVar as [Benign]. Clinvar id is 1284218.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH8	NM_002472.3	c.5568+237del		intron_variant		ENST00000403437.2
MYHAS	NR_125367.1	n.76+9098del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH8	ENST00000403437.2	c.5568+237del		intron_variant		5	NM_002472.3	P1
	ENST00000399342.6	n.76+9098del		intron_variant, non_coding_transcript_variant		3
	ENST00000581304.1	n.52+9098del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19603 AN: 152036 Hom.: 2329 Cov.: 30

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0922

Gnomad ASJ AF: 0.0746

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0777

Gnomad FIN AF: 0.0196

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.0561

Gnomad OTH AF: 0.147

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.129 AC: 19629 AN: 152154 Hom.: 2330 Cov.: 30 AF XY: 0.125 AC XY: 9288 AN XY: 74390

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.0920

Gnomad4 ASJ AF: 0.0746

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0788

Gnomad4 FIN AF: 0.0196

Gnomad4 NFE AF: 0.0561

Gnomad4 OTH AF: 0.145

Alfa AF: 0.0205 Hom.: 13

Bravo AF: 0.143

Asia WGS AF: 0.0490 AC: 169 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 28, 2019

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Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs59406509; hg19: chr17-10295621;