12-110914159-GACACACACAC-GACACACACACACAC

Variant names:

• chr12-110914159-G-GACAC
• rs142567411
• NM_000432.4:c.274+23_274+26dupGTGT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_000432.4(MYL2):​c.274+23_274+26dupGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000407 in 1,376,718 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (2 hom., cov: 31)
  • Exomes 𝑓: 0.00026 (1 hom.)
• Consequence: MYL2 NM_000432.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.360

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-110914159-G-GACAC is Benign according to our data. Variant chr12-110914159-G-GACAC is described in ClinVar as [Benign]. Clinvar id is 1329421.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00161 (241/150138) while in subpopulation AFR AF= 0.00532 (218/40974). AF 95% confidence interval is 0.00474. There are 2 homozygotes in gnomad4. There are 118 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 241 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYL2	NM_000432.4	c.274+23_274+26dupGTGT		intron_variant	Intron 4 of 6	ENST00000228841.15	NP_000423.2
MYL2	NM_001406745.1	c.232+23_232+26dupGTGT		intron_variant	Intron 3 of 5		NP_001393674.1
MYL2	NM_001406916.1	c.217+23_217+26dupGTGT		intron_variant	Intron 4 of 6		NP_001393845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYL2	ENST00000228841.15	c.274+26_274+27insGTGT		intron_variant	Intron 4 of 6	1	NM_000432.4	ENSP00000228841.8
MYL2	ENST00000548438.1	c.232+26_232+27insGTGT		intron_variant	Intron 3 of 5	3		ENSP00000447154.1
MYL2	ENST00000663220.1	c.217+26_217+27insGTGT		intron_variant	Intron 4 of 6			ENSP00000499568.1
MYL2	ENST00000549029.1	n.105+26_105+27insGTGT		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.00155 AC: 233 AN: 150034 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.00514

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000533

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000845

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000148

Gnomad OTH AF: 0.000489

GnomAD4 exome AF: 0.000260 AC: 319 AN: 1226580 Hom.: 1 Cov.: 16 AF XY: 0.000269 AC XY: 166 AN XY: 617332

Gnomad4 AFR exome AF: 0.00491

Gnomad4 AMR exome AF: 0.000217

Gnomad4 ASJ exome AF: 0.0000427

Gnomad4 EAS exome AF: 0.0000273

Gnomad4 SAS exome AF: 0.000448

Gnomad4 FIN exome AF: 0.0000403

Gnomad4 NFE exome AF: 0.000128

Gnomad4 OTH exome AF: 0.000270

GnomAD4 genome AF: 0.00161 AC: 241 AN: 150138 Hom.: 2 Cov.: 31 AF XY: 0.00161 AC XY: 118 AN XY: 73214

Gnomad4 AFR AF: 0.00532

Gnomad4 AMR AF: 0.000532

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000846

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000148

Gnomad4 OTH AF: 0.000484

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cardiomyopathy Benign:1

Sep 30, 2020

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs142567411; hg19: chr12-111351963;