2-210298339-TACACACACACACAC-TACACACACACACACACACACACACAC

Variant names:

• chr2-210298339-T-TACACACACACAC
• rs112894708
• NM_079420.3:c.304+69_304+80dupGTGTGTGTGTGT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_079420.3(MYL1):​c.304+69_304+80dupGTGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000999 in 1,187,610 control chromosomes in the GnomAD database, including 3 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00093 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0010 (3 hom.)
• Consequence: MYL1 NM_079420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• Publications: 0 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: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• congenital myopathy

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ENSG00000279317 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 3 Unknown,AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYL1	NM_079420.3	MANE Select	c.304+69_304+80dupGTGTGTGTGTGT		intron	N/A	NP_524144.1	P05976-1
	MYL1	NM_079422.3		c.172+69_172+80dupGTGTGTGTGTGT		intron	N/A	NP_524146.1	P05976-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYL1	ENST00000352451.4	TSL:1 MANE Select	c.304+80_304+81insGTGTGTGTGTGT		intron	N/A	ENSP00000307280.4	P05976-1
	MYL1	ENST00000341685.8	TSL:1	c.172+80_172+81insGTGTGTGTGTGT		intron	N/A	ENSP00000343321.4	P05976-2
	MYL1	ENST00000957378.1		c.268+80_268+81insGTGTGTGTGTGT		intron	N/A	ENSP00000627437.1

Frequencies

GnomAD3 genomes AF: 0.000930 AC: 137 AN: 147310 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000478

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00136

Gnomad ASJ AF: 0.000292

Gnomad EAS AF: 0.00429

Gnomad SAS AF: 0.00177

Gnomad FIN AF: 0.000609

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000897

Gnomad OTH AF: 0.000988

GnomAD4 exome AF: 0.00101 AC: 1050 AN: 1040192 Hom.: 3 AF XY: 0.00109 AC XY: 578 AN XY: 530236

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000418 AC: 11 AN: 26298

American (AMR) AF: 0.00168 AC: 71 AN: 42206

Ashkenazi Jewish (ASJ) AF: 0.000189 AC: 4 AN: 21208

East Asian (EAS) AF: 0.00322 AC: 115 AN: 35720

South Asian (SAS) AF: 0.00285 AC: 204 AN: 71630

European-Finnish (FIN) AF: 0.000537 AC: 24 AN: 44690

Middle Eastern (MID) AF: 0.000759 AC: 3 AN: 3954

European-Non Finnish (NFE) AF: 0.000768 AC: 575 AN: 748610

Other (OTH) AF: 0.000937 AC: 43 AN: 45876

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000929 AC: 137 AN: 147418 Hom.: 0 Cov.: 0 AF XY: 0.000977 AC XY: 70 AN XY: 71630

African (AFR) AF: 0.000477 AC: 19 AN: 39860

American (AMR) AF: 0.00136 AC: 20 AN: 14728

Ashkenazi Jewish (ASJ) AF: 0.000292 AC: 1 AN: 3430

East Asian (EAS) AF: 0.00430 AC: 21 AN: 4882

South Asian (SAS) AF: 0.00177 AC: 8 AN: 4518

European-Finnish (FIN) AF: 0.000609 AC: 6 AN: 9852

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.000897 AC: 60 AN: 66916

Other (OTH) AF: 0.000977 AC: 2 AN: 2048

Alfa AF: 0.00 Hom.: 299

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs112894708; hg19: chr2-211163063;