rs587781049

Variant names:

• chr16-15745112-T-C
• rs185697714
• NM_002474.3:c.2520+17A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-15745112-T-C
• chrNT_187607.1-1403123-T-C

Variant summary

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

The NM_002474.3(MYH11):​c.2520+17A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00398 in 1,605,218 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0037 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0040 (18 hom.)
• Consequence: MYH11 NM_002474.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -3.09
• Publications: 1 publications found

Genes affected

MYH11 (HGNC:7569): (myosin heavy chain 11) The protein encoded by this gene is a smooth muscle myosin belonging to the myosin heavy chain family. The gene product is a subunit of a hexameric protein that consists of two heavy chain subunits and two pairs of non-identical light chain subunits. It functions as a major contractile protein, converting chemical energy into mechanical energy through the hydrolysis of ATP. A chromosomal rearrangement involving this gene is associated with acute myeloid leukemia of the M4Eo subtype. Mutations in this gene are associated with visceral myopathy, megacystis-microcolon-intestinal hypoperistalsis syndrome 2, and familial thoracic aortic aneurysm 4. [provided by RefSeq, May 2022]

MYH11 Gene-Disease associations (from GenCC):

• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• aortic aneurysm, familial thoracic 4

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• megacystis-microcolon-intestinal hypoperistalsis syndrome 2

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• megacystis-microcolon-intestinal hypoperistalsis syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• visceral myopathy 2

  Inheritance: AR, AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-15745112-T-C is Benign according to our data. Variant chr16-15745112-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 138331.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 = 0.00367 (559/152310) while in subpopulation NFE AF = 0.00426 (290/68024). AF 95% confidence interval is 0.00386. There are 1 homozygotes in GnomAd4. There are 314 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 18 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002474.3. 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
	MYH11	NM_002474.3	MANE Select	c.2520+17A>G		intron	N/A	NP_002465.1
	MYH11	NM_001040113.2	MANE Plus Clinical	c.2541+17A>G		intron	N/A	NP_001035202.1
	MYH11	NM_001040114.2		c.2541+17A>G		intron	N/A	NP_001035203.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH11	ENST00000300036.6	TSL:1 MANE Select	c.2520+17A>G		intron	N/A	ENSP00000300036.5
	MYH11	ENST00000452625.7	TSL:1 MANE Plus Clinical	c.2541+17A>G		intron	N/A	ENSP00000407821.2
	MYH11	ENST00000396324.7	TSL:1	c.2541+17A>G		intron	N/A	ENSP00000379616.3

Frequencies

GnomAD3 genomes AF: 0.00367 AC: 559 AN: 152192 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00360

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0165

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00426

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00370 AC: 929 AN: 251036 AF XY: 0.00391

Gnomad AFR exome AF: 0.000370

Gnomad AMR exome AF: 0.00174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0160

Gnomad NFE exome AF: 0.00443

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00401 AC: 5828 AN: 1452908 Hom.: 18 Cov.: 31 AF XY: 0.00398 AC XY: 2877 AN XY: 723412

African (AFR) AF: 0.000540 AC: 18 AN: 33348

American (AMR) AF: 0.00197 AC: 88 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0000767 AC: 2 AN: 26092

East Asian (EAS) AF: 0.00 AC: 0 AN: 39642

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86108

European-Finnish (FIN) AF: 0.0141 AC: 750 AN: 53174

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00433 AC: 4784 AN: 1103946

Other (OTH) AF: 0.00308 AC: 185 AN: 60126

GnomAD4 genome AF: 0.00367 AC: 559 AN: 152310 Hom.: 1 Cov.: 33 AF XY: 0.00422 AC XY: 314 AN XY: 74482

African (AFR) AF: 0.000722 AC: 30 AN: 41574

American (AMR) AF: 0.00359 AC: 55 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.0165 AC: 175 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00426 AC: 290 AN: 68024

Other (OTH) AF: 0.00426 AC: 9 AN: 2112

Alfa AF: 0.00281 Hom.: 0

Bravo AF: 0.00264

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Aortic aneurysm, familial thoracic 4 (3)
-	-	3	not specified (3)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.47
DANN	Benign	0.39
PhyloP100		-3.1
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: rs185697714; hg19: chr16-15838969;