chr2-210303457-T-TC

Variant names:

• chr2-210303457-T-TC
• rs35179660
• NM_079420.3:c.133-943_133-942insG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_079420.3(MYL1):​c.133-943_133-942insG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 1,336,116 control chromosomes in the GnomAD database, including 100,904 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (12588 hom., cov: 0)
  • Exomes 𝑓: 0.38 (88316 hom.)
• Consequence: MYL1 NM_079420.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.257
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 2-210303457-T-TC is Benign according to our data. Variant chr2-210303457-T-TC is described in ClinVar as Benign. ClinVar VariationId is 1221134.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

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.133-943_133-942insG		intron	N/A	NP_524144.1	P05976-1
	MYL1	NM_079422.3		c.3+84_3+85insG		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.133-943_133-942insG		intron	N/A	ENSP00000307280.4	P05976-1
	MYL1	ENST00000341685.8	TSL:1	c.3+84_3+85insG		intron	N/A	ENSP00000343321.4	P05976-2
	MYL1	ENST00000957378.1		c.133-943_133-942insG		intron	N/A	ENSP00000627437.1

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61511 AN: 151826 Hom.: 12546 Cov.: 0

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.419

GnomAD4 exome AF: 0.377 AC: 446420 AN: 1184172 Hom.: 88316 AF XY: 0.379 AC XY: 225998 AN XY: 596224

African (AFR) AF: 0.387 AC: 10087 AN: 26066

American (AMR) AF: 0.561 AC: 20066 AN: 35746

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 9382 AN: 21942

East Asian (EAS) AF: 0.441 AC: 15930 AN: 36148

South Asian (SAS) AF: 0.456 AC: 32997 AN: 72336

European-Finnish (FIN) AF: 0.447 AC: 22749 AN: 50908

Middle Eastern (MID) AF: 0.503 AC: 2066 AN: 4104

European-Non Finnish (NFE) AF: 0.353 AC: 313402 AN: 886630

Other (OTH) AF: 0.393 AC: 19741 AN: 50292

GnomAD4 genome AF: 0.406 AC: 61616 AN: 151944 Hom.: 12588 Cov.: 0 AF XY: 0.414 AC XY: 30754 AN XY: 74264

African (AFR) AF: 0.391 AC: 16188 AN: 41442

American (AMR) AF: 0.501 AC: 7641 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1520 AN: 3468

East Asian (EAS) AF: 0.450 AC: 2325 AN: 5164

South Asian (SAS) AF: 0.461 AC: 2215 AN: 4808

European-Finnish (FIN) AF: 0.460 AC: 4850 AN: 10548

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.373 AC: 25373 AN: 67938

Other (OTH) AF: 0.419 AC: 884 AN: 2108

Alfa AF: 0.389 Hom.: 1431

Bravo AF: 0.405

Asia WGS AF: 0.497 AC: 1725 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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: rs35179660; hg19: chr2-211168181;