rs2292300

Variant names:

• chr2-210302408-A-T
• rs2292300
• NM_079420.3:c.160+80T>A

Your query was ambiguous. Multiple possible variants found:

• chr2-210302408-A-T
• chr2-210302408-A-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_079420.3(MYL1):​c.160+80T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,347,298 control chromosomes in the GnomAD database, including 102,204 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (12604 hom., cov: 32)
  • Exomes 𝑓: 0.38 (89600 hom.)
• Consequence: MYL1 NM_079420.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.452
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 2-210302408-A-T is Benign according to our data. Variant chr2-210302408-A-T is described in ClinVar as Benign. ClinVar VariationId is 1294855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.160+80T>A		intron	N/A	NP_524144.1	P05976-1
	MYL1	NM_079422.3		c.28+360T>A		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.160+80T>A		intron	N/A	ENSP00000307280.4	P05976-1
	MYL1	ENST00000341685.8	TSL:1	c.28+360T>A		intron	N/A	ENSP00000343321.4	P05976-2
	MYL1	ENST00000957378.1		c.160+80T>A		intron	N/A	ENSP00000627437.1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61577 AN: 151802 Hom.: 12563 Cov.: 32

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.417

GnomAD4 exome AF: 0.383 AC: 458084 AN: 1195378 Hom.: 89600 AF XY: 0.385 AC XY: 229880 AN XY: 597512

African (AFR) AF: 0.391 AC: 10213 AN: 26110

American (AMR) AF: 0.551 AC: 14993 AN: 27188

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 8517 AN: 19772

East Asian (EAS) AF: 0.441 AC: 16152 AN: 36622

South Asian (SAS) AF: 0.456 AC: 29672 AN: 65094

European-Finnish (FIN) AF: 0.448 AC: 22372 AN: 49974

Middle Eastern (MID) AF: 0.527 AC: 2661 AN: 5054

European-Non Finnish (NFE) AF: 0.364 AC: 333294 AN: 914888

Other (OTH) AF: 0.399 AC: 20210 AN: 50676

GnomAD4 genome AF: 0.406 AC: 61681 AN: 151920 Hom.: 12604 Cov.: 32 AF XY: 0.415 AC XY: 30794 AN XY: 74278

African (AFR) AF: 0.391 AC: 16184 AN: 41424

American (AMR) AF: 0.501 AC: 7633 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1521 AN: 3472

East Asian (EAS) AF: 0.452 AC: 2327 AN: 5152

South Asian (SAS) AF: 0.460 AC: 2217 AN: 4818

European-Finnish (FIN) AF: 0.459 AC: 4852 AN: 10560

Middle Eastern (MID) AF: 0.503 AC: 145 AN: 288

European-Non Finnish (NFE) AF: 0.375 AC: 25444 AN: 67934

Other (OTH) AF: 0.418 AC: 885 AN: 2116

Alfa AF: 0.390 Hom.: 1465

Bravo AF: 0.406

Asia WGS AF: 0.498 AC: 1728 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	14
DANN	Benign	0.73
PhyloP100		0.45
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: rs2292300; hg19: chr2-211167132; COSMIC: COSV107429459;