rs76530988

Variant names:

• chr20-31826725-G-A
• rs76530988
• NM_033118.4:c.1082+11G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-31826725-G-A
• chr20-31826725-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000375985.5(MYLK2):​c.1082+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0245 in 1,614,012 control chromosomes in the GnomAD database, including 608 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (42 hom., cov: 31)
  • Exomes 𝑓: 0.025 (566 hom.)
• Consequence: MYLK2 ENST00000375985.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.02
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 20-31826725-G-A is Benign according to our data. Variant chr20-31826725-G-A is described in ClinVar as Benign. ClinVar VariationId is 36649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0192 (2923/152168) while in subpopulation NFE AF = 0.0278 (1890/67988). AF 95% confidence interval is 0.0268. There are 42 homozygotes in GnomAd4. There are 1432 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2923 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000375985.5. 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.1082+11G>A		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.1082+11G>A		intron	N/A	ENSP00000365152.4
	MYLK2	ENST00000375994.6	TSL:1	c.1082+11G>A		intron	N/A	ENSP00000365162.2
	MYLK2	ENST00000468730.1	TSL:1	n.-52G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0192 AC: 2926 AN: 152050 Hom.: 42 Cov.: 31

Gnomad AFR AF: 0.00483

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.0180

Gnomad ASJ AF: 0.0361

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.0367

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0278

Gnomad OTH AF: 0.0168

GnomAD2 exomes AF: 0.0203 AC: 5105 AN: 251324 AF XY: 0.0205

Gnomad AFR exome AF: 0.00499

Gnomad AMR exome AF: 0.0113

Gnomad ASJ exome AF: 0.0372

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0397

Gnomad NFE exome AF: 0.0282

Gnomad OTH exome AF: 0.0227

GnomAD4 exome AF: 0.0250 AC: 36576 AN: 1461844 Hom.: 566 Cov.: 33 AF XY: 0.0244 AC XY: 17719 AN XY: 727216

African (AFR) AF: 0.00436 AC: 146 AN: 33480

American (AMR) AF: 0.0125 AC: 559 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0347 AC: 907 AN: 26132

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00185 AC: 160 AN: 86254

European-Finnish (FIN) AF: 0.0393 AC: 2099 AN: 53414

Middle Eastern (MID) AF: 0.0113 AC: 65 AN: 5768

European-Non Finnish (NFE) AF: 0.0281 AC: 31279 AN: 1111978

Other (OTH) AF: 0.0225 AC: 1359 AN: 60396

GnomAD4 genome AF: 0.0192 AC: 2923 AN: 152168 Hom.: 42 Cov.: 31 AF XY: 0.0192 AC XY: 1432 AN XY: 74404

African (AFR) AF: 0.00479 AC: 199 AN: 41512

American (AMR) AF: 0.0179 AC: 274 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0361 AC: 125 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4806

European-Finnish (FIN) AF: 0.0367 AC: 390 AN: 10614

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0278 AC: 1890 AN: 67988

Other (OTH) AF: 0.0166 AC: 35 AN: 2108

Alfa AF: 0.0220 Hom.: 14

Bravo AF: 0.0178

Asia WGS AF: 0.00202 AC: 8 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	not provided (2)
-	-	1	Cardiomyopathy (1)
-	-	1	Hypertrophic cardiomyopathy 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	10
DANN	Benign	0.51
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs76530988; hg19: chr20-30414528;