rs867853414

Variant names:

• chr12-110910993-G-A
• rs867853414
• NM_000432.4:c.*84C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-110910993-G-A
• chr12-110910993-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000432.4(MYL2):​c.*84C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00000243 in 1,236,510 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 Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: MYL2 NM_000432.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 3.92
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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.*84C>T		3_prime_UTR	Exon 7 of 7	NP_000423.2	P10916
	MYL2	NM_001406745.1		c.*84C>T		3_prime_UTR	Exon 6 of 6	NP_001393674.1	G3V1V8
	MYL2	NM_001406916.1		c.*84C>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.*84C>T		3_prime_UTR	Exon 7 of 7	ENSP00000228841.8	P10916
	MYL2	ENST00000713800.1		c.*84C>T		3_prime_UTR	Exon 8 of 8	ENSP00000519106.1	P10916
	MYL2	ENST00000713803.1		c.*84C>T		3_prime_UTR	Exon 8 of 8	ENSP00000519109.1	P10916

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000184 AC: 2 AN: 1084324 Hom.: 0 Cov.: 15 AF XY: 0.00 AC XY: 0 AN XY: 556066

African (AFR) AF: 0.00 AC: 0 AN: 26144

American (AMR) AF: 0.00 AC: 0 AN: 44088

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23818

East Asian (EAS) AF: 0.00 AC: 0 AN: 37876

South Asian (SAS) AF: 0.00 AC: 0 AN: 78572

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51020

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5028

European-Non Finnish (NFE) AF: 0.00000260 AC: 2 AN: 769724

Other (OTH) AF: 0.00 AC: 0 AN: 48054

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74348

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15272

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Hypertrophic cardiomyopathy 10 (1)
-	1	-	Hypertrophic cardiomyopathy 10;C5561937:Myopathy, myofibrillar, 12, infantile-onset, with cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.3
DANN	Benign	0.64
PhyloP100		3.9
Mutation Taster		=100/0	polymorphism

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: rs867853414; hg19: chr12-111348797;