2-210302991-C-A

Variant names:

• chr2-210302991-C-A
• rs16844288
• NM_079420.3:c.133-476G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_079420.3(MYL1):​c.133-476G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYL1 NM_079420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.793
• Publications: 1 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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.133-476G>T		intron	N/A	NP_524144.1	P05976-1
	MYL1	NM_079422.3		c.4-199G>T		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.133-476G>T		intron	N/A	ENSP00000307280.4	P05976-1
	MYL1	ENST00000341685.8	TSL:1	c.4-199G>T		intron	N/A	ENSP00000343321.4	P05976-2
	MYL1	ENST00000957378.1		c.133-476G>T		intron	N/A	ENSP00000627437.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 434770 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 228078

African (AFR) AF: 0.00 AC: 0 AN: 11886

American (AMR) AF: 0.00 AC: 0 AN: 16096

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13302

East Asian (EAS) AF: 0.00 AC: 0 AN: 30176

South Asian (SAS) AF: 0.00 AC: 0 AN: 39136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1892

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 261772

Other (OTH) AF: 0.00 AC: 0 AN: 25182

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 580

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.85
DANN	Benign	0.13
PhyloP100		-0.79

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: rs16844288; hg19: chr2-211167715;