2-210302991-C-T

Position:

• chr2-210302991-C-T

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.133-476G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 586,034 control chromosomes in the GnomAD database, including 48,728 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (12616 hom., cov: 32)
  • Exomes 𝑓: 0.40 (36112 hom.)
• Consequence: MYL1 NM_079420.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.793

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 2-210302991-C-T is Benign according to our data. Variant chr2-210302991-C-T is described in ClinVar as [Benign]. Clinvar id is 1294865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYL1	NM_079420.3	c.133-476G>A		intron_variant		ENST00000352451.4
MYL1	NM_079422.3	c.4-199G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYL1	ENST00000352451.4	c.133-476G>A		intron_variant		1	NM_079420.3
MYL1	ENST00000341685.8	c.4-199G>A		intron_variant		1		P1
MYL1	ENST00000484290.1	n.75-35G>A		intron_variant, non_coding_transcript_variant		5
MYL1	ENST00000496436.5	n.75-35G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61611 AN: 151844 Hom.: 12574 Cov.: 32

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.417

GnomAD4 exome AF: 0.403 AC: 174783 AN: 434072 Hom.: 36112 Cov.: 4 AF XY: 0.404 AC XY: 92032 AN XY: 227714

Gnomad4 AFR exome AF: 0.394

Gnomad4 AMR exome AF: 0.534

Gnomad4 ASJ exome AF: 0.431

Gnomad4 EAS exome AF: 0.450

Gnomad4 SAS exome AF: 0.461

Gnomad4 FIN exome AF: 0.449

Gnomad4 NFE exome AF: 0.372

Gnomad4 OTH exome AF: 0.406

GnomAD4 genome AF: 0.406 AC: 61716 AN: 151962 Hom.: 12616 Cov.: 32 AF XY: 0.415 AC XY: 30793 AN XY: 74276

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.438

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.460

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.418

Alfa AF: 0.244 Hom.: 580

Bravo AF: 0.406

Asia WGS AF: 0.497 AC: 1725 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	1.1
DANN	Benign	0.13

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: rs16844288; hg19: chr2-211167715;