rs2136457

Variant names:

• chr2-210292725-T-C
• rs2136457
• NM_079420.3:c.556+998A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-210292725-T-C
• chr2-210292725-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_079420.3(MYL1):​c.556+998A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 151,992 control chromosomes in the GnomAD database, including 19,963 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (19963 hom., cov: 32)
• Consequence: MYL1 NM_079420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.654
• Publications: 2 publications found

Genes affected

MYL1 (HGNC:7582): (myosin light chain 1) Myosin is a hexameric ATPase cellular motor protein. It is composed of two heavy chains, two nonphosphorylatable alkali light chains, and two phosphorylatable regulatory light chains. This gene encodes a myosin alkali light chain expressed in fast skeletal muscle. Two transcript variants have been identified for this gene. [provided by RefSeq, Jul 2008]

MYL1 Gene-Disease associations (from GenCC):

• congenital myopathy with reduced type 2 muscle fibers

  Inheritance: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P
• congenital myopathy

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ENSG00000279317 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_079420.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYL1	NM_079420.3	MANE Select	c.556+998A>G		intron	N/A	NP_524144.1
	MYL1	NM_079422.3		c.424+998A>G		intron	N/A	NP_524146.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYL1	ENST00000352451.4	TSL:1 MANE Select	c.556+998A>G		intron	N/A	ENSP00000307280.4
	MYL1	ENST00000341685.8	TSL:1	c.424+998A>G		intron	N/A	ENSP00000343321.4
	MYL1	ENST00000496436.5	TSL:5	n.659+998A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77707 AN: 151874 Hom.: 19914 Cov.: 32

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.527

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

GnomAD4 genome AF: 0.512 AC: 77815 AN: 151992 Hom.: 19963 Cov.: 32 AF XY: 0.517 AC XY: 38423 AN XY: 74302

African (AFR) AF: 0.544 AC: 22564 AN: 41454

American (AMR) AF: 0.584 AC: 8916 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2084 AN: 3470

East Asian (EAS) AF: 0.451 AC: 2333 AN: 5168

South Asian (SAS) AF: 0.541 AC: 2610 AN: 4822

European-Finnish (FIN) AF: 0.503 AC: 5307 AN: 10544

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.474 AC: 32203 AN: 67946

Other (OTH) AF: 0.526 AC: 1109 AN: 2108

Alfa AF: 0.494 Hom.: 2338

Bravo AF: 0.517

Asia WGS AF: 0.537 AC: 1861 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.30
DANN	Benign	0.37
PhyloP100		-0.65
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: rs2136457; hg19: chr2-211157449;