19-10775530-G-T

Position:

• chr19-10775530-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001005361.3(DNM2):​c.386-173G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 152,040 control chromosomes in the GnomAD database, including 8,952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.32 (8952 hom., cov: 32)
• Consequence: DNM2 NM_001005361.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.335

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 19-10775530-G-T is Benign according to our data. Variant chr19-10775530-G-T is described in ClinVar as [Benign]. Clinvar id is 679310.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNM2	NM_001005361.3	c.386-173G>T		intron_variant		ENST00000389253.9	NP_001005361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNM2	ENST00000389253.9	c.386-173G>T		intron_variant		5	NM_001005361.3	ENSP00000373905	A1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48956 AN: 151922 Hom.: 8949 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.336

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

GnomAD4 genome AF: 0.322 AC: 48969 AN: 152040 Hom.: 8952 Cov.: 32 AF XY: 0.318 AC XY: 23645 AN XY: 74298

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.273

Gnomad4 ASJ AF: 0.436

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.308

Gnomad4 FIN AF: 0.370

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.334

Alfa AF: 0.413 Hom.: 17440

Bravo AF: 0.309

Asia WGS AF: 0.243 AC: 848 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.38
DANN	Benign	0.42

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

Other links and lift over

dbSNP: rs4804528; hg19: chr19-10886206;