2-210298339-TACACACACACACAC-TACACACACAC

Variant names:

• chr2-210298339-TACAC-T
• rs112894708
• NM_079420.3:c.304+77_304+80delGTGT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_079420.3(MYL1):​c.304+77_304+80delGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 1,152,542 control chromosomes in the GnomAD database, including 58 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.014 (46 hom., cov: 0)
  • Exomes 𝑓: 0.029 (12 hom.)
• Consequence: MYL1 NM_079420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0137 (2025/147316) while in subpopulation AFR AF = 0.0449 (1788/39858). AF 95% confidence interval is 0.0431. There are 46 homozygotes in GnomAd4. There are 962 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 46 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+77_304+80delGTGT		intron	N/A	NP_524144.1	P05976-1
	MYL1	NM_079422.3		c.172+77_172+80delGTGT		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+77_304+80delGTGT		intron	N/A	ENSP00000307280.4	P05976-1
	MYL1	ENST00000341685.8	TSL:1	c.172+77_172+80delGTGT		intron	N/A	ENSP00000343321.4	P05976-2
	MYL1	ENST00000957378.1		c.268+77_268+80delGTGT		intron	N/A	ENSP00000627437.1

Frequencies

GnomAD3 genomes AF: 0.0137 AC: 2022 AN: 147208 Hom.: 45 Cov.: 0

Gnomad AFR AF: 0.0449

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00510

Gnomad ASJ AF: 0.000583

Gnomad EAS AF: 0.00368

Gnomad SAS AF: 0.00840

Gnomad FIN AF: 0.000509

Gnomad MID AF: 0.00323

Gnomad NFE AF: 0.00109

Gnomad OTH AF: 0.0124

GnomAD4 exome AF: 0.0294 AC: 29602 AN: 1005226 Hom.: 12 AF XY: 0.0293 AC XY: 15020 AN XY: 512110

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

African (AFR) AF: 0.0489 AC: 1269 AN: 25938

American (AMR) AF: 0.0197 AC: 808 AN: 41054

Ashkenazi Jewish (ASJ) AF: 0.0183 AC: 379 AN: 20688

East Asian (EAS) AF: 0.0184 AC: 642 AN: 34820

South Asian (SAS) AF: 0.0287 AC: 1997 AN: 69462

European-Finnish (FIN) AF: 0.0305 AC: 1293 AN: 42330

Middle Eastern (MID) AF: 0.0131 AC: 51 AN: 3884

European-Non Finnish (NFE) AF: 0.0303 AC: 21907 AN: 722670

Other (OTH) AF: 0.0283 AC: 1256 AN: 44380

⚠️ 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: 0.0137 AC: 2025 AN: 147316 Hom.: 46 Cov.: 0 AF XY: 0.0134 AC XY: 962 AN XY: 71570

African (AFR) AF: 0.0449 AC: 1788 AN: 39858

American (AMR) AF: 0.00510 AC: 75 AN: 14716

Ashkenazi Jewish (ASJ) AF: 0.000583 AC: 2 AN: 3430

East Asian (EAS) AF: 0.00369 AC: 18 AN: 4882

South Asian (SAS) AF: 0.00841 AC: 38 AN: 4518

European-Finnish (FIN) AF: 0.000509 AC: 5 AN: 9816

Middle Eastern (MID) AF: 0.00347 AC: 1 AN: 288

European-Non Finnish (NFE) AF: 0.00109 AC: 73 AN: 66866

Other (OTH) AF: 0.0122 AC: 25 AN: 2046

Alfa AF: 0.00 Hom.: 299

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism

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: rs112894708; hg19: chr2-211163063;