19-10799277-C-T

Variant names:

• chr19-10799277-C-T
• rs11881315
• NM_001005361.3:c.1422+705C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001005360.3(DNM2):​c.1422+705C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,020 control chromosomes in the GnomAD database, including 2,415 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.17 (2415 hom., cov: 31)
• Consequence: DNM2 NM_001005360.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• Publications: 14 publications found

Genes affected

DNM2 (HGNC:2974): (dynamin 2) Dynamins represent one of the subfamilies of GTP-binding proteins. These proteins share considerable sequence similarity over the N-terminal portion of the molecule, which contains the GTPase domain. Dynamins are associated with microtubules. They have been implicated in cell processes such as endocytosis and cell motility, and in alterations of the membrane that accompany certain activities such as bone resorption by osteoclasts. Dynamins bind many proteins that bind actin and other cytoskeletal proteins. Dynamins can also self-assemble, a process that stimulates GTPase activity. Five alternatively spliced transcripts encoding different proteins have been described. Additional alternatively spliced transcripts may exist, but their full-length nature has not been determined. [provided by RefSeq, Jun 2010]

DNM2 Gene-Disease associations (from GenCC):

• autosomal dominant centronuclear myopathy

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Charcot-Marie-Tooth disease

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Charcot-Marie-Tooth disease dominant intermediate B

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• autosomal dominant Charcot-Marie-Tooth disease type 2M

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• fetal akinesia-cerebral and retinal hemorrhage syndrome

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• hereditary spastic paraplegia

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005360.3. 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
	DNM2	NM_001005361.3	MANE Select	c.1422+705C>T		intron	N/A	NP_001005361.1
	DNM2	NM_001005360.3		c.1422+705C>T		intron	N/A	NP_001005360.1
	DNM2	NM_001190716.2		c.1422+705C>T		intron	N/A	NP_001177645.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNM2	ENST00000389253.9	TSL:5 MANE Select	c.1422+705C>T		intron	N/A	ENSP00000373905.4
	DNM2	ENST00000355667.11	TSL:1	c.1422+705C>T		intron	N/A	ENSP00000347890.6
	DNM2	ENST00000585892.5	TSL:1	c.1422+705C>T		intron	N/A	ENSP00000468734.1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26552 AN: 151902 Hom.: 2410 Cov.: 31

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.168

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.175 AC: 26592 AN: 152020 Hom.: 2415 Cov.: 31 AF XY: 0.177 AC XY: 13179 AN XY: 74324

African (AFR) AF: 0.173 AC: 7189 AN: 41458

American (AMR) AF: 0.138 AC: 2108 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.210 AC: 728 AN: 3470

East Asian (EAS) AF: 0.159 AC: 818 AN: 5152

South Asian (SAS) AF: 0.128 AC: 617 AN: 4826

European-Finnish (FIN) AF: 0.203 AC: 2153 AN: 10596

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12313 AN: 67940

Other (OTH) AF: 0.169 AC: 358 AN: 2116

Alfa AF: 0.177 Hom.: 1315

Bravo AF: 0.172

Asia WGS AF: 0.135 AC: 470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.59
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11881315; hg19: chr19-10909953;