Variant rs572538551 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_000432.4(MYL2):c.274+8_274+9insAT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000244 in 1,599,588 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

MYL2
NM_000432.4 splice_region, intron

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.27

Variant links:

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 links:

MYL2 (HGNC:):

MYL2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
MYL2	NM_000432.4 linkuse as main transcript	c.274+8_274+9insAT	splice_region_variant, intron_variant	ENST00000228841.15	NP_000423.2	P10916Q6IB42
MYL2	NM_001406745.1 linkuse as main transcript	c.232+8_232+9insAT	splice_region_variant, intron_variant		NP_001393674.1
MYL2	NM_001406916.1 linkuse as main transcript	c.217+8_217+9insAT	splice_region_variant, intron_variant		NP_001393845.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MYL2	ENST00000228841.15 linkuse as main transcript	c.274+8_274+9insAT	splice_region_variant, intron_variant	1	NM_000432.4	ENSP00000228841.8	P10916
MYL2	ENST00000548438.1 linkuse as main transcript	c.232+8_232+9insAT	splice_region_variant, intron_variant	3		ENSP00000447154.1	G3V1V8
MYL2	ENST00000663220.1 linkuse as main transcript	c.217+8_217+9insAT	splice_region_variant, intron_variant			ENSP00000499568.1	A0A590UJU8
MYL2	ENST00000549029.1 linkuse as main transcript	n.105+8_105+9insAT	splice_region_variant, intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0000461

AC:

AN:

151980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000517

AC:

AN:

251454

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000221

AC:

AN:

1447608

Hom.:

Cov.:

AF XY:

0.0000305

AC XY:

AN XY:

721220

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000314

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000668

GnomAD4 genome

AF:

0.0000461

AC:

AN:

151980

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hypertrophic cardiomyopathy 10

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 20, 2023

This sequence change falls in intron 4 of the MYL2 gene. It does not directly change the encoded amino acid sequence of the MYL2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs572538551, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with MYL2-related conditions. ClinVar contains an entry for this variant (Variation ID: 409233). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over