20-31832151-A-T

Variant names:

• chr20-31832151-A-T
• rs6060980
• NM_033118.4:c.1710+15A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_033118.4(MYLK2):​c.1710+15A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00069 (0 hom., cov: 32)
  • Exomes 𝑓: 0.037 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYLK2 NM_033118.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0320
• Publications: 8 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 20-31832151-A-T is Benign according to our data. Variant chr20-31832151-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1667218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYLK2	NM_033118.4	MANE Select	c.1710+15A>T		intron	N/A	NP_149109.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYLK2	ENST00000375985.5	TSL:1 MANE Select	c.1710+15A>T		intron	N/A	ENSP00000365152.4
	MYLK2	ENST00000375994.6	TSL:1	c.1710+15A>T		intron	N/A	ENSP00000365162.2
	MYLK2	ENST00000468730.1	TSL:1	n.648+15A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000687 AC: 99 AN: 144160 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000520

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000956

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00386

Gnomad SAS AF: 0.00377

Gnomad FIN AF: 0.000871

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.000494

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0371 AC: 28835 AN: 777568 Hom.: 0 Cov.: 26 AF XY: 0.0351 AC XY: 14179 AN XY: 404050

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0334 AC: 721 AN: 21614

American (AMR) AF: 0.0141 AC: 546 AN: 38650

Ashkenazi Jewish (ASJ) AF: 0.0434 AC: 774 AN: 17822

East Asian (EAS) AF: 0.0632 AC: 1362 AN: 21550

South Asian (SAS) AF: 0.00636 AC: 448 AN: 70398

European-Finnish (FIN) AF: 0.0139 AC: 532 AN: 38228

Middle Eastern (MID) AF: 0.0268 AC: 114 AN: 4248

European-Non Finnish (NFE) AF: 0.0429 AC: 22804 AN: 531948

Other (OTH) AF: 0.0463 AC: 1534 AN: 33110

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000686 AC: 99 AN: 144322 Hom.: 0 Cov.: 32 AF XY: 0.000896 AC XY: 63 AN XY: 70304

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000543 AC: 22 AN: 40506

American (AMR) AF: 0.000954 AC: 14 AN: 14678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3348

East Asian (EAS) AF: 0.00362 AC: 15 AN: 4146

South Asian (SAS) AF: 0.00376 AC: 15 AN: 3990

European-Finnish (FIN) AF: 0.000871 AC: 8 AN: 9182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.000368 AC: 24 AN: 65274

Other (OTH) AF: 0.000488 AC: 1 AN: 2048

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.0010
DANN	Benign	0.39
PhyloP100		-0.032
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs6060980; hg19: chr20-30419954;