rs147463138

Variant names:

• chr19-10830148-G-A
• rs147463138
• NM_001005361.3:c.2313G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-10830148-G-A
• chr19-10830148-G-C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001005361.3(DNM2):​c.2313G>A​(p.Pro771Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000191 in 1,613,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: DNM2 NM_001005361.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -2.92
• Publications: 1 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: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Orphanet
• 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: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• hereditary spastic paraplegia

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 19-10830148-G-A is Benign according to our data. Variant chr19-10830148-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 327988.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.92 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNM2	NM_001005361.3	MANE Select	c.2313G>A	p.Pro771Pro	synonymous	Exon 20 of 21	NP_001005361.1	P50570-4
	DNM2	NM_001005360.3		c.2313G>A	p.Pro771Pro	synonymous	Exon 20 of 21	NP_001005360.1	P50570-1
	DNM2	NM_001190716.2		c.2313G>A	p.Pro771Pro	synonymous	Exon 20 of 21	NP_001177645.1	P50570-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNM2	ENST00000389253.9	TSL:5 MANE Select	c.2313G>A	p.Pro771Pro	synonymous	Exon 20 of 21	ENSP00000373905.4	P50570-4
	DNM2	ENST00000355667.11	TSL:1	c.2313G>A	p.Pro771Pro	synonymous	Exon 20 of 21	ENSP00000347890.6	P50570-1
	DNM2	ENST00000585892.5	TSL:1	c.2313G>A	p.Pro771Pro	synonymous	Exon 20 of 21	ENSP00000468734.1	P50570-5

Frequencies

GnomAD3 genomes AF: 0.0000921 AC: 14 AN: 152048 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000116 AC: 29 AN: 249988 AF XY: 0.000111

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000205

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000201 AC: 294 AN: 1461660 Hom.: 0 Cov.: 32 AF XY: 0.000195 AC XY: 142 AN XY: 727148

African (AFR) AF: 0.0000597 AC: 2 AN: 33476

American (AMR) AF: 0.0000224 AC: 1 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.000237 AC: 264 AN: 1111864

Other (OTH) AF: 0.000348 AC: 21 AN: 60376

GnomAD4 genome AF: 0.0000921 AC: 14 AN: 152048 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74274

African (AFR) AF: 0.0000725 AC: 3 AN: 41378

American (AMR) AF: 0.00 AC: 0 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67972

Other (OTH) AF: 0.000479 AC: 1 AN: 2088

Alfa AF: 0.000196 Hom.: 0

Bravo AF: 0.0000831

EpiCase AF: 0.000327

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Charcot-Marie-Tooth disease dominant intermediate B (2)
-	-	1	Autosomal dominant centronuclear myopathy (1)
-	-	1	DNM2-related disorder (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.43
DANN	Benign	0.82
PhyloP100		-2.9
PromoterAI		0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs147463138; hg19: chr19-10940824;