rs2229920

Variant names:

• chr19-10829116-T-C
• rs2229920
• NM_001005361.3:c.2139T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-10829116-T-C
• chr19-10829116-T-G
• chr19-10829116-T-A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001005361.3(DNM2):​c.2139T>C​(p.Ala713Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 1,613,602 control chromosomes in the GnomAD database, including 78,330 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A713A) has been classified as Likely benign. The gene DNM2 is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.30 (7084 hom., cov: 33)
  • Exomes 𝑓: 0.31 (71246 hom.)
• Consequence: DNM2 NM_001005361.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: -4.76
• Publications: 32 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]

MIR6793 (HGNC:50251): (microRNA 6793) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Specifications for DNM2 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 19-10829116-T-C is Benign according to our data. Variant chr19-10829116-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 158523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.76 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.561 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNM2	NM_001005361.3	MANE Select	c.2139T>C	p.Ala713Ala	synonymous	Exon 19 of 21	NP_001005361.1	P50570-4
	DNM2	NM_001005360.3		c.2139T>C	p.Ala713Ala	synonymous	Exon 19 of 21	NP_001005360.1	P50570-1
	DNM2	NM_001190716.2		c.2139T>C	p.Ala713Ala	synonymous	Exon 19 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.2139T>C	p.Ala713Ala	synonymous	Exon 19 of 21	ENSP00000373905.4	P50570-4
	DNM2	ENST00000355667.11	TSL:1	c.2139T>C	p.Ala713Ala	synonymous	Exon 19 of 21	ENSP00000347890.6	P50570-1
	DNM2	ENST00000585892.5	TSL:1	c.2139T>C	p.Ala713Ala	synonymous	Exon 19 of 21	ENSP00000468734.1	P50570-5

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45622 AN: 151982 Hom.: 7058 Cov.: 33

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.296

GnomAD2 exomes AF: 0.312 AC: 78204 AN: 250390 AF XY: 0.313

Gnomad AFR exome AF: 0.281

Gnomad AMR exome AF: 0.256

Gnomad ASJ exome AF: 0.319

Gnomad EAS exome AF: 0.564

Gnomad FIN exome AF: 0.321

Gnomad NFE exome AF: 0.291

Gnomad OTH exome AF: 0.313

GnomAD4 exome AF: 0.308 AC: 449698 AN: 1461502 Hom.: 71246 Cov.: 56 AF XY: 0.307 AC XY: 223397 AN XY: 727050

African (AFR) AF: 0.281 AC: 9419 AN: 33474

American (AMR) AF: 0.255 AC: 11413 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 8182 AN: 26134

East Asian (EAS) AF: 0.576 AC: 22875 AN: 39682

South Asian (SAS) AF: 0.309 AC: 26645 AN: 86238

European-Finnish (FIN) AF: 0.317 AC: 16909 AN: 53272

Middle Eastern (MID) AF: 0.337 AC: 1943 AN: 5768

European-Non Finnish (NFE) AF: 0.300 AC: 333313 AN: 1111880

Other (OTH) AF: 0.315 AC: 18999 AN: 60382

GnomAD4 genome AF: 0.300 AC: 45696 AN: 152100 Hom.: 7084 Cov.: 33 AF XY: 0.305 AC XY: 22708 AN XY: 74356

African (AFR) AF: 0.280 AC: 11622 AN: 41502

American (AMR) AF: 0.271 AC: 4150 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1074 AN: 3468

East Asian (EAS) AF: 0.578 AC: 2981 AN: 5158

South Asian (SAS) AF: 0.303 AC: 1461 AN: 4822

European-Finnish (FIN) AF: 0.342 AC: 3621 AN: 10582

Middle Eastern (MID) AF: 0.360 AC: 105 AN: 292

European-Non Finnish (NFE) AF: 0.291 AC: 19768 AN: 67964

Other (OTH) AF: 0.297 AC: 628 AN: 2112

Alfa AF: 0.288 Hom.: 15448

Bravo AF: 0.298

Asia WGS AF: 0.419 AC: 1459 AN: 3478

EpiCase AF: 0.303

EpiControl AF: 0.296

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	not specified (7)
-	-	2	Charcot-Marie-Tooth disease dominant intermediate B (2)
-	-	2	not provided (2)
-	-	1	Autosomal dominant centronuclear myopathy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.45
PhyloP100		-4.8
PromoterAI		-0.00020	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=96/4	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: rs2229920; hg19: chr19-10939792; COSMIC: COSV53033084; COSMIC: COSV53033084;