rs2233260

Variant names:

• chr12-110913195-G-A
• rs2233260
• NM_000432.4:c.353+51C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-110913195-G-A
• chr12-110913195-G-C
• chr12-110913195-G-T

Variant summary

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

The NM_000432.4(MYL2):​c.353+51C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,613,166 control chromosomes in the GnomAD database, including 45,790 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3694 hom., cov: 33)
  • Exomes 𝑓: 0.23 (42096 hom.)
• Consequence: MYL2 NM_000432.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 O:1
• Conservation: PhyloP100: -0.211
• Publications: 8 publications found

Genes affected

MYL2 (HGNC:7583): (myosin light chain 2) This gene encodes a major sarcomeric protein in mammalian striated muscle. The encoded protein plays a role in embryonic heart muscle structure and function, while phosphorylation of the encoded protein is involved in cardiac myosin cycling kinetics, torsion and function in adults. Mutations in this gene are associated with hypertrophic cardiomyopathy 10 and infant-onset myopathy. [provided by RefSeq, May 2022]

MYL2 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• hypertrophic cardiomyopathy 10

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• myopathy, myofibrillar, 12, infantile-onset, with cardiomyopathy

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• congenital fiber-type disproportion myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• arrhythmogenic right ventricular cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 12-110913195-G-A is Benign according to our data. Variant chr12-110913195-G-A is described in ClinVar as Benign. ClinVar VariationId is 31774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYL2	NM_000432.4	c.353+51C>T		intron_variant	Intron 5 of 6	ENST00000228841.15	NP_000423.2
MYL2	NM_001406745.1	c.311+51C>T		intron_variant	Intron 4 of 5		NP_001393674.1
MYL2	NM_001406916.1	c.296+51C>T		intron_variant	Intron 5 of 6		NP_001393845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYL2	ENST00000228841.15	c.353+51C>T		intron_variant	Intron 5 of 6	1	NM_000432.4	ENSP00000228841.8

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32017 AN: 151328 Hom.: 3690 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.00423

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.213

GnomAD2 exomes AF: 0.210 AC: 52206 AN: 248922 AF XY: 0.205

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.324

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.00273

Gnomad FIN exome AF: 0.265

Gnomad NFE exome AF: 0.234

Gnomad OTH exome AF: 0.220

GnomAD4 exome AF: 0.232 AC: 338628 AN: 1461718 Hom.: 42096 Cov.: 38 AF XY: 0.227 AC XY: 164966 AN XY: 727160

African (AFR) AF: 0.147 AC: 4929 AN: 33480

American (AMR) AF: 0.322 AC: 14397 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 3079 AN: 26134

East Asian (EAS) AF: 0.00194 AC: 77 AN: 39700

South Asian (SAS) AF: 0.126 AC: 10842 AN: 86246

European-Finnish (FIN) AF: 0.265 AC: 14151 AN: 53420

Middle Eastern (MID) AF: 0.156 AC: 902 AN: 5768

European-Non Finnish (NFE) AF: 0.249 AC: 277000 AN: 1111862

Other (OTH) AF: 0.219 AC: 13251 AN: 60394

GnomAD4 genome AF: 0.211 AC: 32023 AN: 151448 Hom.: 3694 Cov.: 33 AF XY: 0.210 AC XY: 15570 AN XY: 74050

African (AFR) AF: 0.158 AC: 6428 AN: 40788

American (AMR) AF: 0.279 AC: 4268 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 380 AN: 3464

East Asian (EAS) AF: 0.00444 AC: 23 AN: 5186

South Asian (SAS) AF: 0.111 AC: 534 AN: 4824

European-Finnish (FIN) AF: 0.275 AC: 2911 AN: 10592

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16681 AN: 67992

Other (OTH) AF: 0.211 AC: 445 AN: 2112

Alfa AF: 0.230 Hom.: 3556

Bravo AF: 0.214

ClinVar

Significance: Benign

Submissions summary: Benign:2 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2 Other:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 26, 2012

Leiden Muscular Dystrophy (MYL2)

Significance: not provided

Review Status: no classification provided

Collection Method: curation

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.61
DANN	Benign	0.56
PhyloP100		-0.21
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: rs2233260; hg19: chr12-111350999; COSMIC: COSV57406861;