2-210292725-T-C

Position:

• chr2-210292725-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_079420.3(MYL1):​c.556+998A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 151,992 control chromosomes in the GnomAD database, including 19,963 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (19963 hom., cov: 32)
• Consequence: MYL1 NM_079420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.654

Genes affected

MYL1 (HGNC:7582): (myosin light chain 1) Myosin is a hexameric ATPase cellular motor protein. It is composed of two heavy chains, two nonphosphorylatable alkali light chains, and two phosphorylatable regulatory light chains. This gene encodes a myosin alkali light chain expressed in fast skeletal muscle. Two transcript variants have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYL1	NM_079420.3	c.556+998A>G		intron_variant		ENST00000352451.4
MYL1	NM_079422.3	c.424+998A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYL1	ENST00000352451.4	c.556+998A>G		intron_variant		1	NM_079420.3
MYL1	ENST00000341685.8	c.424+998A>G		intron_variant		1		P1
MYL1	ENST00000496436.5	n.659+998A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77707 AN: 151874 Hom.: 19914 Cov.: 32

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.527

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.512 AC: 77815 AN: 151992 Hom.: 19963 Cov.: 32 AF XY: 0.517 AC XY: 38423 AN XY: 74302

Gnomad4 AFR AF: 0.544

Gnomad4 AMR AF: 0.584

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.526

Alfa AF: 0.494 Hom.: 2338

Bravo AF: 0.517

Asia WGS AF: 0.537 AC: 1861 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.30
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs2136457; hg19: chr2-211157449;