chr19-10727001-G-A

Variant names:

• chr19-10727001-G-A
• rs892086
• NM_001005361.3:c.161+8598G>A

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+8598G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 152,016 control chromosomes in the GnomAD database, including 26,943 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 0.59 (26943 hom., cov: 32)
• Consequence: DNM2 NM_001005361.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.188
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005361.3. 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.161+8598G>A		intron	N/A	NP_001005361.1
	DNM2	NM_001005360.3		c.161+8598G>A		intron	N/A	NP_001005360.1
	DNM2	NM_001190716.2		c.161+8598G>A		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.161+8598G>A		intron	N/A	ENSP00000373905.4
	DNM2	ENST00000355667.11	TSL:1	c.161+8598G>A		intron	N/A	ENSP00000347890.6
	DNM2	ENST00000585892.5	TSL:1	c.161+8598G>A		intron	N/A	ENSP00000468734.1

Frequencies

GnomAD3 genomes AF: 0.594 AC: 90188 AN: 151898 Hom.: 26938 Cov.: 32

Gnomad AFR AF: 0.636

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.594 AC: 90230 AN: 152016 Hom.: 26943 Cov.: 32 AF XY: 0.593 AC XY: 44076 AN XY: 74306

African (AFR) AF: 0.635 AC: 26299 AN: 41420

American (AMR) AF: 0.602 AC: 9178 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1905 AN: 3470

East Asian (EAS) AF: 0.465 AC: 2406 AN: 5174

South Asian (SAS) AF: 0.651 AC: 3145 AN: 4832

European-Finnish (FIN) AF: 0.552 AC: 5832 AN: 10564

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39640 AN: 67986

Other (OTH) AF: 0.566 AC: 1198 AN: 2116

Alfa AF: 0.583 Hom.: 44658

Bravo AF: 0.593

Asia WGS AF: 0.581 AC: 2021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	13
DANN	Benign	0.80
PhyloP100		-0.19
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: rs892086; hg19: chr19-10837677;