12-110919198-G-A

Position:

• chr12-110919198-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000432.4(MYL2):​c.4-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYL2 NM_000432.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00005256
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.187

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 12-110919198-G-A is Benign according to our data. Variant chr12-110919198-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 415511.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYL2	NM_000432.4	c.4-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000228841.15	NP_000423.2
MYL2	NM_001406745.1	c.4-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001393674.1
MYL2	NM_001406916.1	c.-54-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001393845.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYL2	ENST00000228841.15	c.4-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000432.4	ENSP00000228841	P1
MYL2	ENST00000546404.1	c.4-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2		ENSP00000499645
MYL2	ENST00000548438.1	c.4-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		3		ENSP00000447154
MYL2	ENST00000663220.1	c.-54-5C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant				ENSP00000499568

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hypertrophic cardiomyopathy 10 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 02, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.6
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000053
dbscSNV1_RF	Benign	0.0020
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

Publications

LitVar

Other links and lift over

dbSNP: rs374870836; hg19: chr12-111357002;