rs747642850

Variant names:

• chr16-15708848-CAGAG-C
• rs747642850
• NM_002474.3:c.5787-4729_5787-4726delCTCT

Your query was ambiguous. Multiple possible variants found:

• chr16-15708848-CAGAG-C
• chr16-15708848-CAGAG-CAG

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS1

The NM_002474.3(MYH11):​c.5787-4729_5787-4726delCTCT variant causes a intron change. The variant allele was found at a frequency of 0.000424 in 1,609,690 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00043 (0 hom.)
• Consequence: MYH11 NM_002474.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 6.42
• Publications: 0 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]

NDE1 (HGNC:17619): (nudE neurodevelopment protein 1) This gene encodes a member of the nuclear distribution E (NudE) family of proteins. The encoded protein is localized at the centrosome and interacts with other centrosome components as part of a multiprotein complex that regulates dynein function. This protein plays an essential role in microtubule organization, mitosis and neuronal migration. Mutations in this gene cause lissencephaly 4, a disorder characterized by lissencephaly, severe brain atrophy, microcephaly, and severe cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

NDE1 Gene-Disease associations (from GenCC):

• lissencephaly 4

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: PanelApp Australia, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• hydranencephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• microlissencephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• NDE1-related microhydranencephaly

  Inheritance: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP6: Variant 16-15708848-CAGAG-C is Benign according to our data. Variant chr16-15708848-CAGAG-C is described in ClinVar as [Likely_benign]. Clinvar id is 201040.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000414 (63/152264) while in subpopulation AMR AF = 0.00118 (18/15286). AF 95% confidence interval is 0.000761. There are 0 homozygotes in GnomAd4. There are 34 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH11	NM_002474.3	c.5787-4729_5787-4726delCTCT		intron_variant	Intron 40 of 40	ENST00000300036.6	NP_002465.1
MYH11	NM_001040113.2	c.5808-11_5808-8delCTCT		splice_region_variant, intron_variant	Intron 41 of 42	ENST00000452625.7	NP_001035202.1
NDE1	NM_017668.3	c.947+11994_947+11997delGAGA		intron_variant	Intron 8 of 8	ENST00000396354.6	NP_060138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH11	ENST00000300036.6	c.5787-4729_5787-4726delCTCT		intron_variant	Intron 40 of 40	1	NM_002474.3	ENSP00000300036.5
MYH11	ENST00000452625.7	c.5808-11_5808-8delCTCT		splice_region_variant, intron_variant	Intron 41 of 42	1	NM_001040113.2	ENSP00000407821.2
NDE1	ENST00000396354.6	c.947+11989_947+11992delAGAG		intron_variant	Intron 8 of 8	1	NM_017668.3	ENSP00000379642.1

Frequencies

GnomAD3 genomes AF: 0.000414 AC: 63 AN: 152146 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000420 AC: 102 AN: 242886 AF XY: 0.000427

Gnomad AFR exome AF: 0.000197

Gnomad AMR exome AF: 0.000743

Gnomad ASJ exome AF: 0.000102

Gnomad EAS exome AF: 0.000222

Gnomad FIN exome AF: 0.0000948

Gnomad NFE exome AF: 0.000537

Gnomad OTH exome AF: 0.000168

GnomAD4 exome AF: 0.000425 AC: 620 AN: 1457426 Hom.: 0 AF XY: 0.000418 AC XY: 303 AN XY: 724386

African (AFR) AF: 0.000359 AC: 12 AN: 33450

American (AMR) AF: 0.000591 AC: 26 AN: 44010

Ashkenazi Jewish (ASJ) AF: 0.0000385 AC: 1 AN: 25952

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39648

South Asian (SAS) AF: 0.000377 AC: 32 AN: 84970

European-Finnish (FIN) AF: 0.0000753 AC: 4 AN: 53128

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5760

European-Non Finnish (NFE) AF: 0.000466 AC: 517 AN: 1110230

Other (OTH) AF: 0.000332 AC: 20 AN: 60278

GnomAD4 genome AF: 0.000414 AC: 63 AN: 152264 Hom.: 0 Cov.: 32 AF XY: 0.000457 AC XY: 34 AN XY: 74442

African (AFR) AF: 0.000409 AC: 17 AN: 41564

American (AMR) AF: 0.00118 AC: 18 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

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

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000174 Hom.: 0

Bravo AF: 0.000465

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Familial thoracic aortic aneurysm and aortic dissection Benign:3

Jan 11, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The variant is found in TAAD panel(s). -

Sep 29, 2018

Color Diagnostics, LLC DBA Color Health

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 29, 2022

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Jul 08, 2024

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aortic aneurysm, familial thoracic 4 Benign:1

Jan 15, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jun 20, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Connective tissue disorder Benign:1

Jun 01, 2018

Center for Human Genetics, Inc, Center for Human Genetics, Inc

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.4
Mutation Taster		=99/1	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: rs747642850; hg19: chr16-15802705;