rs149164657

Variant names:

• chr19-10829038-G-A
• rs149164657
• NM_001005361.3:c.2061G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-10829038-G-A
• chr19-10829038-G-T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001005361.3(DNM2):​c.2061G>A​(p.Thr687Thr) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000753 in 1,612,714 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T687T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00096 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00073 (2 hom.)
• Consequence: DNM2 NM_001005361.3 splice_region, synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -3.92
• Publications: 0 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

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 19-10829038-G-A is Benign according to our data. Variant chr19-10829038-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 327986.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.92 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

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.2061G>A	p.Thr687Thr	splice_region synonymous	Exon 19 of 21	NP_001005361.1	P50570-4
	DNM2	NM_001005360.3		c.2061G>A	p.Thr687Thr	splice_region synonymous	Exon 19 of 21	NP_001005360.1	P50570-1
	DNM2	NM_001190716.2		c.2061G>A	p.Thr687Thr	splice_region 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.2061G>A	p.Thr687Thr	splice_region synonymous	Exon 19 of 21	ENSP00000373905.4	P50570-4
	DNM2	ENST00000355667.11	TSL:1	c.2061G>A	p.Thr687Thr	splice_region synonymous	Exon 19 of 21	ENSP00000347890.6	P50570-1
	DNM2	ENST00000585892.5	TSL:1	c.2061G>A	p.Thr687Thr	splice_region synonymous	Exon 19 of 21	ENSP00000468734.1	P50570-5

Frequencies

GnomAD3 genomes AF: 0.000959 AC: 146 AN: 152184 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00952

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00124 AC: 306 AN: 247486 AF XY: 0.00124

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00871

Gnomad NFE exome AF: 0.000988

Gnomad OTH exome AF: 0.00149

GnomAD4 exome AF: 0.000732 AC: 1069 AN: 1460412 Hom.: 2 Cov.: 31 AF XY: 0.000702 AC XY: 510 AN XY: 726412

African (AFR) AF: 0.0000598 AC: 2 AN: 33426

American (AMR) AF: 0.00 AC: 0 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86036

European-Finnish (FIN) AF: 0.00818 AC: 433 AN: 52954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.000520 AC: 578 AN: 1111526

Other (OTH) AF: 0.000912 AC: 55 AN: 60328

GnomAD4 genome AF: 0.000959 AC: 146 AN: 152302 Hom.: 2 Cov.: 32 AF XY: 0.00128 AC XY: 95 AN XY: 74472

African (AFR) AF: 0.000120 AC: 5 AN: 41582

American (AMR) AF: 0.0000654 AC: 1 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00952 AC: 101 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 68010

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000424 Hom.: 0

Bravo AF: 0.000223

EpiCase AF: 0.000273

EpiControl AF: 0.000476

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)
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Autosomal dominant centronuclear myopathy (1)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.070
DANN	Benign	0.83
PhyloP100		-3.9
PromoterAI		-0.0052	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs149164657; hg19: chr19-10939714;