19-10724729-C-T

Variant names:

• chr19-10724729-C-T
• rs714307
• NM_001005361.3:c.161+6326C>T

Variant summary

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

The NM_001005361.3(DNM2):​c.161+6326C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 152,086 control chromosomes in the GnomAD database, including 36,621 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 0.69 (36621 hom., cov: 32)
• Consequence: DNM2 NM_001005361.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.265
• Publications: 8 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNM2	NM_001005361.3	c.161+6326C>T		intron_variant	Intron 1 of 20	ENST00000389253.9	NP_001005361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNM2	ENST00000389253.9	c.161+6326C>T		intron_variant	Intron 1 of 20	5	NM_001005361.3	ENSP00000373905.4

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104735 AN: 151968 Hom.: 36585 Cov.: 32

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.725

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.837

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.676

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

GnomAD4 genome AF: 0.689 AC: 104826 AN: 152086 Hom.: 36621 Cov.: 32 AF XY: 0.693 AC XY: 51518 AN XY: 74334

African (AFR) AF: 0.779 AC: 32329 AN: 41514

American (AMR) AF: 0.725 AC: 11078 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2210 AN: 3470

East Asian (EAS) AF: 0.837 AC: 4317 AN: 5156

South Asian (SAS) AF: 0.759 AC: 3663 AN: 4824

European-Finnish (FIN) AF: 0.641 AC: 6774 AN: 10568

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.623 AC: 42351 AN: 67966

Other (OTH) AF: 0.674 AC: 1423 AN: 2112

Alfa AF: 0.642 Hom.: 121058

Bravo AF: 0.696

Asia WGS AF: 0.802 AC: 2788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.5
DANN	Benign	0.37
PhyloP100		0.27
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: rs714307; hg19: chr19-10835405;