rs2270056

Variant names:

• chr17-10392180-C-T
• rs2270056
• NM_002472.3:c.5569-203G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-10392180-C-T
• chr17-10392180-C-G

Variant summary

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

The NM_002472.3(MYH8):​c.5569-203G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 151,996 control chromosomes in the GnomAD database, including 26,118 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.57 (26118 hom., cov: 32)
• Consequence: MYH8 NM_002472.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.594
• Publications: 3 publications found

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]

MYHAS (HGNC:50609): (myosin heavy chain gene cluster antisense RNA) Predicted to enable primary miRNA binding activity. Predicted to be involved in response to muscle activity and skeletal muscle fiber development. Predicted to act upstream of or within with a positive effect on gene expression. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-10392180-C-T is Benign according to our data. Variant chr17-10392180-C-T is described in ClinVar as Benign. ClinVar VariationId is 1243083.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002472.3. 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
	MYH8	NM_002472.3	MANE Select	c.5569-203G>A		intron	N/A	NP_002463.2	P13535
	MYHAS	NR_125367.1		n.76+8973C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH8	ENST00000403437.2	TSL:5 MANE Select	c.5569-203G>A		intron	N/A	ENSP00000384330.2	P13535
	MYHAS	ENST00000399342.6	TSL:3	n.76+8973C>T		intron	N/A
	MYHAS	ENST00000581304.2	TSL:3	n.52+8973C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87311 AN: 151878 Hom.: 26097 Cov.: 32

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.575 AC: 87380 AN: 151996 Hom.: 26118 Cov.: 32 AF XY: 0.561 AC XY: 41696 AN XY: 74270

African (AFR) AF: 0.685 AC: 28419 AN: 41482

American (AMR) AF: 0.505 AC: 7711 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1863 AN: 3466

East Asian (EAS) AF: 0.133 AC: 687 AN: 5168

South Asian (SAS) AF: 0.333 AC: 1603 AN: 4816

European-Finnish (FIN) AF: 0.518 AC: 5456 AN: 10530

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.585 AC: 39726 AN: 67954

Other (OTH) AF: 0.603 AC: 1275 AN: 2114

Alfa AF: 0.576 Hom.: 40699

Bravo AF: 0.583

Asia WGS AF: 0.275 AC: 961 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.54
DANN	Benign	0.37
PhyloP100		-0.59
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: rs2270056; hg19: chr17-10295497;