16-15703925-G-GT

Variant names:

• chr16-15703925-G-GT
• rs5815842
• NM_002474.3:c.*65dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002474.3(MYH11):​c.*65dupA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00498 in 1,606,278 control chromosomes in the GnomAD database, including 333 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.027 (178 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (155 hom.)
• Consequence: MYH11 NM_002474.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.794
• 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]

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 -10 ACMG points.

• BP6: Variant 16-15703925-G-GT is Benign according to our data. Variant chr16-15703925-G-GT is described in ClinVar as [Benign]. Clinvar id is 1294395.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH11	NM_002474.3	c.*65dupA		3_prime_UTR_variant	Exon 41 of 41	ENST00000300036.6	NP_002465.1
MYH11	NM_001040113.2	c.*206dupA		3_prime_UTR_variant	Exon 43 of 43	ENST00000452625.7	NP_001035202.1
NDE1	NM_017668.3	c.947+7073dupT		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.*65dupA		3_prime_UTR_variant	Exon 41 of 41	1	NM_002474.3	ENSP00000300036.5
MYH11	ENST00000452625.7	c.*206dupA		3_prime_UTR_variant	Exon 43 of 43	1	NM_001040113.2	ENSP00000407821.2
NDE1	ENST00000396354.6	c.947+7073dupT		intron_variant	Intron 8 of 8	1	NM_017668.3	ENSP00000379642.1

Frequencies

GnomAD3 genomes AF: 0.0270 AC: 4098 AN: 151678 Hom.: 178 Cov.: 32

Gnomad AFR AF: 0.0948

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00933

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0168

GnomAD2 exomes AF: 0.00697 AC: 1742 AN: 249778 AF XY: 0.00520

Gnomad AFR exome AF: 0.0952

Gnomad AMR exome AF: 0.00489

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000168

Gnomad OTH exome AF: 0.00197

GnomAD4 exome AF: 0.00267 AC: 3889 AN: 1454482 Hom.: 155 Cov.: 30 AF XY: 0.00226 AC XY: 1634 AN XY: 723972

African (AFR) AF: 0.0929 AC: 3093 AN: 33286

American (AMR) AF: 0.00537 AC: 240 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26078

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39574

South Asian (SAS) AF: 0.000303 AC: 26 AN: 85800

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 53034

Middle Eastern (MID) AF: 0.00247 AC: 14 AN: 5672

European-Non Finnish (NFE) AF: 0.000136 AC: 151 AN: 1106286

Other (OTH) AF: 0.00598 AC: 359 AN: 60080

GnomAD4 genome AF: 0.0271 AC: 4110 AN: 151796 Hom.: 178 Cov.: 32 AF XY: 0.0257 AC XY: 1905 AN XY: 74206

African (AFR) AF: 0.0949 AC: 3921 AN: 41324

American (AMR) AF: 0.00926 AC: 141 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10546

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

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67956

Other (OTH) AF: 0.0166 AC: 35 AN: 2110

Alfa AF: 0.00123 Hom.: 3

Bravo AF: 0.0311

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 11, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.79
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: rs5815842; hg19: chr16-15797782;