2-210303622-A-G

Variant names:

• chr2-210303622-A-G
• rs12469767
• ENST00000341685.8:c.-78T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000341685.8(MYL1):​c.-78T>C variant causes a 5 prime UTR 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: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYL1 ENST00000341685.8 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.69
• Publications: 10 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000341685.8. 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.133-1107T>C		intron	N/A	NP_524144.1	P05976-1
	MYL1	NM_079422.3		c.-78T>C		upstream_gene	N/A	NP_524146.1	P05976-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYL1	ENST00000341685.8	TSL:1	c.-78T>C		5_prime_UTR	Exon 1 of 7	ENSP00000343321.4	P05976-2
	MYL1	ENST00000352451.4	TSL:1 MANE Select	c.133-1107T>C		intron	N/A	ENSP00000307280.4	P05976-1
	MYL1	ENST00000957378.1		c.133-1107T>C		intron	N/A	ENSP00000627437.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1429118 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 710344

African (AFR) AF: 0.00 AC: 0 AN: 31438

American (AMR) AF: 0.00 AC: 0 AN: 37894

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24374

East Asian (EAS) AF: 0.00 AC: 0 AN: 38294

South Asian (SAS) AF: 0.00 AC: 0 AN: 81088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52658

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5598

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1098924

Other (OTH) AF: 0.00 AC: 0 AN: 58850

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 6728

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	16
DANN	Benign	0.78
PhyloP100		1.7
PromoterAI		-0.026	Neutral
Mutation Taster		=284/16	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: rs12469767; hg19: chr2-211168346;