chr2-210298274-G-A

Position:

• chr2-210298274-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_079420.3(MYL1):​c.304+146C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 933,002 control chromosomes in the GnomAD database, including 102,774 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (16768 hom., cov: 28)
  • Exomes 𝑓: 0.46 (86006 hom.)
• Consequence: MYL1 NM_079420.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.670

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-210298274-G-A is Benign according to our data. Variant chr2-210298274-G-A is described in ClinVar as [Benign]. Clinvar id is 1225443.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYL1	NM_079420.3	c.304+146C>T		intron_variant		ENST00000352451.4
MYL1	NM_079422.3	c.172+146C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYL1	ENST00000352451.4	c.304+146C>T		intron_variant		1	NM_079420.3
MYL1	ENST00000341685.8	c.172+146C>T		intron_variant		1		P1
MYL1	ENST00000484290.1	n.435+146C>T		intron_variant, non_coding_transcript_variant		5
MYL1	ENST00000496436.5	n.407+146C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.469 AC: 70819 AN: 151128 Hom.: 16725 Cov.: 28

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.493

GnomAD4 exome AF: 0.464 AC: 362939 AN: 781756 Hom.: 86006 AF XY: 0.466 AC XY: 183396 AN XY: 393414

Gnomad4 AFR exome AF: 0.389

Gnomad4 AMR exome AF: 0.598

Gnomad4 ASJ exome AF: 0.561

Gnomad4 EAS exome AF: 0.438

Gnomad4 SAS exome AF: 0.520

Gnomad4 FIN exome AF: 0.479

Gnomad4 NFE exome AF: 0.453

Gnomad4 OTH exome AF: 0.484

GnomAD4 genome AF: 0.469 AC: 70919 AN: 151246 Hom.: 16768 Cov.: 28 AF XY: 0.475 AC XY: 35039 AN XY: 73818

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.450

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.492

Alfa AF: 0.467 Hom.: 2082

Bravo AF: 0.469

Asia WGS AF: 0.525 AC: 1824 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.97
DANN	Benign	0.59

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: rs7592060; hg19: chr2-211162998;