Genetic Variant ENST00000341685.8:c.2T>C (chr2-210303543-A-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP6BS2

The ENST00000341685.8(MYL1):c.2T>C(p.Met1?) variant causes a start lost, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000401 in 1,611,430 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0020 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 2 hom. )

Consequence

MYL1
ENST00000341685.8 start_lost, splice_region

Scores

Splicing: ADA: 0.06650

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 7.65

Publications

0 publications found

Variant links:

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

MYL1 links:

ENSG00000279317 (HGNC:):

ENSG00000279317 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP6

Variant 2-210303543-A-G is Benign according to our data. Variant chr2-210303543-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3041875.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 2 Unknown,AR gene

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.133-1028T>C		intron	N/A	NP_524144.1	P05976-1
	MYL1	NM_079422.3		c.2T>C	p.Met1?	start_lost splice_region	Exon 1 of 7	NP_524146.1	P05976-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYL1	ENST00000341685.8	TSL:1	c.2T>C	p.Met1?	start_lost splice_region	Exon 1 of 7	ENSP00000343321.4	P05976-2
MYL1	ENST00000352451.4	TSL:1 MANE Select	c.133-1028T>C		intron	N/A	ENSP00000307280.4	P05976-1
MYL1	ENST00000957378.1		c.133-1028T>C		intron	N/A	ENSP00000627437.1

Frequencies

GnomAD3 genomes

AF:

0.00197

AC:

300

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00690

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000548

AC:

136

AN:

248352

AF XY:

0.000461

show subpopulations

Gnomad AFR exome

AF:

0.00655

Gnomad AMR exome

AF:

0.000502

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000553

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000801

Gnomad OTH exome

AF:

0.000664

GnomAD4 exome

AF:

0.000238

AC:

347

AN:

1459140

Hom.:

Cov.:

AF XY:

0.000216

AC XY:

157

AN XY:

725902

show subpopulations

African (AFR)

AF:

0.00655

AC:

218

AN:

33280

American (AMR)

AF:

0.000652

AC:

AN:

44472

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26066

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39410

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85960

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53352

Middle Eastern (MID)

AF:

0.000696

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.0000612

AC:

AN:

1110602

Other (OTH)

AF:

0.000432

AC:

AN:

60250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00196

AC:

299

AN:

152290

Hom.:

Cov.:

AF XY:

0.00208

AC XY:

155

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00686

AC:

285

AN:

41562

American (AMR)

AF:

0.000785

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000634

Hom.:

Bravo

AF:

0.00207

ESP6500AA

AF:

0.00613

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000782

AC:

EpiCase

AF:

0.0000550

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

MYL1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.15

CADD

Benign

(source)

DANN

Uncertain

0.98

Eigen

Benign

0.089

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

M_CAP

Pathogenic

0.40

MetaRNN

Benign

0.026

MetaSVM

Benign

-0.61

PhyloP100

7.6

PROVEAN

Benign

-0.43

REVEL

Uncertain

0.35

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0080

Polyphen

0.0050

Vest4

0.88

MVP

0.77

ClinPred

0.056

GERP RS

5.6

PromoterAI

-0.019

Neutral

(source)

Mutation Taster

=33/167

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.067

dbscSNV1_RF

Benign

0.39

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over