19-10806008-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001005361.3(DNM2):​c.1545+41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,613,244 control chromosomes in the GnomAD database, including 24,287 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1613 hom., cov: 32)
Exomes 𝑓: 0.17 ( 22674 hom. )

Consequence

DNM2
NM_001005361.3 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.79
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant 19-10806008-C-T is Benign according to our data. Variant chr19-10806008-C-T is described in ClinVar as [Benign]. Clinvar id is 256865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNM2NM_001005361.3 linkc.1545+41C>T intron_variant ENST00000389253.9 NP_001005361.1 P50570-4Q8N1K8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNM2ENST00000389253.9 linkc.1545+41C>T intron_variant 5 NM_001005361.3 ENSP00000373905.4 P50570-4

Frequencies

GnomAD3 genomes
AF:
0.130
AC:
19810
AN:
152070
Hom.:
1613
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0367
Gnomad AMI
AF:
0.261
Gnomad AMR
AF:
0.123
Gnomad ASJ
AF:
0.199
Gnomad EAS
AF:
0.168
Gnomad SAS
AF:
0.127
Gnomad FIN
AF:
0.155
Gnomad MID
AF:
0.225
Gnomad NFE
AF:
0.177
Gnomad OTH
AF:
0.132
GnomAD3 exomes
AF:
0.147
AC:
36851
AN:
250128
Hom.:
2972
AF XY:
0.151
AC XY:
20475
AN XY:
135320
show subpopulations
Gnomad AFR exome
AF:
0.0353
Gnomad AMR exome
AF:
0.0900
Gnomad ASJ exome
AF:
0.204
Gnomad EAS exome
AF:
0.154
Gnomad SAS exome
AF:
0.143
Gnomad FIN exome
AF:
0.141
Gnomad NFE exome
AF:
0.176
Gnomad OTH exome
AF:
0.165
GnomAD4 exome
AF:
0.172
AC:
251988
AN:
1461056
Hom.:
22674
Cov.:
32
AF XY:
0.172
AC XY:
125123
AN XY:
726856
show subpopulations
Gnomad4 AFR exome
AF:
0.0320
Gnomad4 AMR exome
AF:
0.0908
Gnomad4 ASJ exome
AF:
0.202
Gnomad4 EAS exome
AF:
0.164
Gnomad4 SAS exome
AF:
0.145
Gnomad4 FIN exome
AF:
0.138
Gnomad4 NFE exome
AF:
0.184
Gnomad4 OTH exome
AF:
0.161
GnomAD4 genome
AF:
0.130
AC:
19807
AN:
152188
Hom.:
1613
Cov.:
32
AF XY:
0.132
AC XY:
9807
AN XY:
74392
show subpopulations
Gnomad4 AFR
AF:
0.0366
Gnomad4 AMR
AF:
0.123
Gnomad4 ASJ
AF:
0.199
Gnomad4 EAS
AF:
0.169
Gnomad4 SAS
AF:
0.127
Gnomad4 FIN
AF:
0.155
Gnomad4 NFE
AF:
0.177
Gnomad4 OTH
AF:
0.134
Alfa
AF:
0.172
Hom.:
4068
Bravo
AF:
0.125
Asia WGS
AF:
0.123
AC:
431
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJun 26, 2018- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.050
DANN
Benign
0.71
RBP_binding_hub_radar
0.67
RBP_regulation_power_radar
3.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2287029; hg19: chr19-10916684; COSMIC: COSV58958640; COSMIC: COSV58958640; API