2-210298339-TACACACACACACAC-TACACACACACACACACACACACACACACACACAC

Variant names:

• chr2-210298339-T-TACACACACACACACACACAC
• rs112894708
• NM_079420.3:c.304+61_304+80dupGTGTGTGTGTGTGTGTGTGT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_079420.3(MYL1):​c.304+61_304+80dupGTGTGTGTGTGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000961 in 1,040,408 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 0)
  • Exomes 𝑓: 9.6e-7 (0 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: Uncertain_significance. The variant received 0 ACMG points.

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+61_304+80dupGTGTGTGTGTGTGTGTGTGT		intron	N/A	NP_524144.1	P05976-1
	MYL1	NM_079422.3		c.172+61_172+80dupGTGTGTGTGTGTGTGTGTGT		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+81insGTGTGTGTGTGTGTGTGTGT		intron	N/A	ENSP00000307280.4	P05976-1
	MYL1	ENST00000341685.8	TSL:1	c.172+80_172+81insGTGTGTGTGTGTGTGTGTGT		intron	N/A	ENSP00000343321.4	P05976-2
	MYL1	ENST00000957378.1		c.268+80_268+81insGTGTGTGTGTGTGTGTGTGT		intron	N/A	ENSP00000627437.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 9.61e-7 AC: 1 AN: 1040408 Hom.: 0 AF XY: 0.00000189 AC XY: 1 AN XY: 530350

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

African (AFR) AF: 0.00 AC: 0 AN: 26302

American (AMR) AF: 0.00 AC: 0 AN: 42218

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21212

East Asian (EAS) AF: 0.00 AC: 0 AN: 35754

South Asian (SAS) AF: 0.00 AC: 0 AN: 71676

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44692

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3954

European-Non Finnish (NFE) AF: 0.00000134 AC: 1 AN: 748716

Other (OTH) AF: 0.00 AC: 0 AN: 45884

⚠️ 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 Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.7

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;