20-31819410-T-C

Variant names:

• chr20-31819410-T-C
• rs1887731
• NM_033118.4:c.-67T>C

Variant summary

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

The NM_033118.4(MYLK2):​c.-67T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0997 in 830,218 control chromosomes in the GnomAD database, including 4,780 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.081 (660 hom., cov: 32)
  • Exomes 𝑓: 0.10 (4120 hom.)
• Consequence: MYLK2 NM_033118.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.819

Genes affected

MYLK2 (HGNC:16243): (myosin light chain kinase 2) This gene encodes a myosin light chain kinase, a calcium/calmodulin dependent enzyme, that is exclusively expressed in adult skeletal muscle. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 20-31819410-T-C is Benign according to our data. Variant chr20-31819410-T-C is described in ClinVar as [Benign]. Clinvar id is 138405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYLK2	NM_033118.4	c.-67T>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 13	ENST00000375985.5	NP_149109.1
MYLK2	NM_033118.4	c.-67T>C		5_prime_UTR_variant	Exon 1 of 13	ENST00000375985.5	NP_149109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYLK2	ENST00000375985	c.-67T>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 13	1	NM_033118.4	ENSP00000365152.4
MYLK2	ENST00000375994	c.-171T>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 12	1		ENSP00000365162.2
MYLK2	ENST00000375985	c.-67T>C		5_prime_UTR_variant	Exon 1 of 13	1	NM_033118.4	ENSP00000365152.4
MYLK2	ENST00000375994	c.-171T>C		5_prime_UTR_variant	Exon 1 of 12	1		ENSP00000365162.2

Frequencies

GnomAD3 genomes AF: 0.0814 AC: 12371 AN: 151896 Hom.: 661 Cov.: 32

Gnomad AFR AF: 0.0216

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0824

Gnomad ASJ AF: 0.0747

Gnomad EAS AF: 0.00406

Gnomad SAS AF: 0.0940

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.0976

GnomAD4 exome AF: 0.104 AC: 70428 AN: 678204 Hom.: 4120 Cov.: 9 AF XY: 0.105 AC XY: 37394 AN XY: 357320

Gnomad4 AFR exome AF: 0.0206

Gnomad4 AMR exome AF: 0.0711

Gnomad4 ASJ exome AF: 0.0744

Gnomad4 EAS exome AF: 0.00116

Gnomad4 SAS exome AF: 0.106

Gnomad4 FIN exome AF: 0.121

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.0976

GnomAD4 genome AF: 0.0814 AC: 12371 AN: 152014 Hom.: 660 Cov.: 32 AF XY: 0.0816 AC XY: 6065 AN XY: 74308

Gnomad4 AFR AF: 0.0216

Gnomad4 AMR AF: 0.0823

Gnomad4 ASJ AF: 0.0747

Gnomad4 EAS AF: 0.00388

Gnomad4 SAS AF: 0.0945

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.116

Gnomad4 OTH AF: 0.0994

Alfa AF: 0.102 Hom.: 264

Bravo AF: 0.0738

Asia WGS AF: 0.0580 AC: 203 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Nov 22, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	11
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1887731; hg19: chr20-30407213;