20-31826818-C-T

Variant names:

• chr20-31826818-C-T
• rs6089088
• NM_033118.4:c.1104C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_033118.4(MYLK2):​c.1104C>T​(p.Phe368Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0232 in 1,614,006 control chromosomes in the GnomAD database, including 543 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (35 hom., cov: 31)
  • Exomes 𝑓: 0.024 (508 hom.)
• Consequence: MYLK2 NM_033118.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.247
• Publications: 6 publications found

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]

MYLK2 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy 1

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 20-31826818-C-T is Benign according to our data. Variant chr20-31826818-C-T is described in ClinVar as Benign. ClinVar VariationId is 46518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.247 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0174 (2642/152166) while in subpopulation NFE AF = 0.0249 (1692/68004). AF 95% confidence interval is 0.0239. There are 35 homozygotes in GnomAd4. There are 1300 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2642 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033118.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYLK2	NM_033118.4	MANE Select	c.1104C>T	p.Phe368Phe	synonymous	Exon 8 of 13	NP_149109.1	Q9H1R3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYLK2	ENST00000375985.5	TSL:1 MANE Select	c.1104C>T	p.Phe368Phe	synonymous	Exon 8 of 13	ENSP00000365152.4	Q9H1R3
	MYLK2	ENST00000375994.6	TSL:1	c.1104C>T	p.Phe368Phe	synonymous	Exon 7 of 12	ENSP00000365162.2	Q9H1R3
	MYLK2	ENST00000468730.1	TSL:1	n.42C>T		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes AF: 0.0174 AC: 2645 AN: 152048 Hom.: 35 Cov.: 31

Gnomad AFR AF: 0.00491

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.00790

Gnomad FIN AF: 0.0347

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0249

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.0207 AC: 5206 AN: 251280 AF XY: 0.0203

Gnomad AFR exome AF: 0.00357

Gnomad AMR exome AF: 0.0340

Gnomad ASJ exome AF: 0.00298

Gnomad EAS exome AF: 0.000435

Gnomad FIN exome AF: 0.0332

Gnomad NFE exome AF: 0.0242

Gnomad OTH exome AF: 0.0196

GnomAD4 exome AF: 0.0238 AC: 34837 AN: 1461840 Hom.: 508 Cov.: 33 AF XY: 0.0234 AC XY: 17043 AN XY: 727218

African (AFR) AF: 0.00341 AC: 114 AN: 33480

American (AMR) AF: 0.0304 AC: 1358 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00329 AC: 86 AN: 26136

East Asian (EAS) AF: 0.000479 AC: 19 AN: 39698

South Asian (SAS) AF: 0.0110 AC: 953 AN: 86248

European-Finnish (FIN) AF: 0.0327 AC: 1747 AN: 53418

Middle Eastern (MID) AF: 0.00832 AC: 48 AN: 5768

European-Non Finnish (NFE) AF: 0.0264 AC: 29369 AN: 1111992

Other (OTH) AF: 0.0189 AC: 1143 AN: 60394

GnomAD4 genome AF: 0.0174 AC: 2642 AN: 152166 Hom.: 35 Cov.: 31 AF XY: 0.0175 AC XY: 1300 AN XY: 74396

African (AFR) AF: 0.00489 AC: 203 AN: 41500

American (AMR) AF: 0.0190 AC: 291 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5180

South Asian (SAS) AF: 0.00770 AC: 37 AN: 4808

European-Finnish (FIN) AF: 0.0347 AC: 368 AN: 10600

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0249 AC: 1692 AN: 68004

Other (OTH) AF: 0.0109 AC: 23 AN: 2110

Alfa AF: 0.0224 Hom.: 84

Bravo AF: 0.0152

Asia WGS AF: 0.00462 AC: 17 AN: 3478

EpiCase AF: 0.0225

EpiControl AF: 0.0221

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Hypertrophic cardiomyopathy 1 (2)
-	-	2	not specified (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	9.4
DANN	Benign	0.73
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6089088; hg19: chr20-30414621;