12-110910950-G-A

Variant names:

• chr12-110910950-G-A
• rs546464364
• NM_000432.4:c.*127C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_000432.4(MYL2):​c.*127C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000987 in 881,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000048 (0 hom.)
• Consequence: MYL2 NM_000432.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.138
• Publications: 0 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: Labcorp Genetics (formerly Invitae), G2P
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 12-110910950-G-A is Benign according to our data. Variant chr12-110910950-G-A is described in ClinVar as Benign. ClinVar VariationId is 1246380.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000341 (52/152330) while in subpopulation AFR AF = 0.00123 (51/41584). AF 95% confidence interval is 0.000958. There are 0 homozygotes in GnomAd4. There are 20 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000432.4. 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
	MYL2	NM_000432.4	MANE Select	c.*127C>T		3_prime_UTR	Exon 7 of 7	NP_000423.2	P10916
	MYL2	NM_001406745.1		c.*127C>T		3_prime_UTR	Exon 6 of 6	NP_001393674.1	G3V1V8
	MYL2	NM_001406916.1		c.*127C>T		3_prime_UTR	Exon 7 of 7	NP_001393845.1	A0A590UJU8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYL2	ENST00000228841.15	TSL:1 MANE Select	c.*127C>T		3_prime_UTR	Exon 7 of 7	ENSP00000228841.8	P10916
	MYL2	ENST00000713800.1		c.*127C>T		3_prime_UTR	Exon 8 of 8	ENSP00000519106.1	P10916
	MYL2	ENST00000713803.1		c.*127C>T		3_prime_UTR	Exon 8 of 8	ENSP00000519109.1	P10916

Frequencies

GnomAD3 genomes AF: 0.000342 AC: 52 AN: 152212 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000480 AC: 35 AN: 729226 Hom.: 0 Cov.: 10 AF XY: 0.0000362 AC XY: 14 AN XY: 386736

African (AFR) AF: 0.00138 AC: 27 AN: 19626

American (AMR) AF: 0.000101 AC: 4 AN: 39458

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21126

East Asian (EAS) AF: 0.0000281 AC: 1 AN: 35606

South Asian (SAS) AF: 0.00 AC: 0 AN: 69484

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42992

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4054

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 460404

Other (OTH) AF: 0.0000822 AC: 3 AN: 36476

GnomAD4 genome AF: 0.000341 AC: 52 AN: 152330 Hom.: 0 Cov.: 31 AF XY: 0.000268 AC XY: 20 AN XY: 74496

African (AFR) AF: 0.00123 AC: 51 AN: 41584

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000641 Hom.: 0

Bravo AF: 0.000374

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.63
PhyloP100		0.14

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: rs546464364; hg19: chr12-111348754;