12-110914159-GACACACACAC-GACAC

Variant names:

• chr12-110914159-GACACAC-G
• NM_000432.4:c.274+21_274+26delGTGTGT

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000432.4(MYL2):​c.274+21_274+26delGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000326 in 1,226,710 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000033 (0 hom.)
• Consequence: MYL2 NM_000432.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.609

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYL2	NM_000432.4	c.274+21_274+26delGTGTGT		intron_variant	Intron 4 of 6	ENST00000228841.15	NP_000423.2
MYL2	NM_001406745.1	c.232+21_232+26delGTGTGT		intron_variant	Intron 3 of 5		NP_001393674.1
MYL2	NM_001406916.1	c.217+21_217+26delGTGTGT		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+21_274+26delGTGTGT		intron_variant	Intron 4 of 6	1	NM_000432.4	ENSP00000228841.8
MYL2	ENST00000548438.1	c.232+21_232+26delGTGTGT		intron_variant	Intron 3 of 5	3		ENSP00000447154.1
MYL2	ENST00000663220.1	c.217+21_217+26delGTGTGT		intron_variant	Intron 4 of 6			ENSP00000499568.1
MYL2	ENST00000549029.1	n.105+21_105+26delGTGTGT		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000326 AC: 4 AN: 1226710 Hom.: 0 AF XY: 0.00000648 AC XY: 4 AN XY: 617382

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000329

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-111351963;