rs10404348

Positions:

• chr19-10729525-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001005361.3(DNM2):​c.161+11122A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 151,872 control chromosomes in the GnomAD database, including 25,707 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (25707 hom., cov: 31)
• Consequence: DNM2 NM_001005361.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.346

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNM2	NM_001005361.3	c.161+11122A>G		intron_variant		ENST00000389253.9	NP_001005361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNM2	ENST00000389253.9	c.161+11122A>G		intron_variant		5	NM_001005361.3	ENSP00000373905	A1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88064 AN: 151754 Hom.: 25704 Cov.: 31

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.580 AC: 88084 AN: 151872 Hom.: 25707 Cov.: 31 AF XY: 0.580 AC XY: 43046 AN XY: 74216

Gnomad4 AFR AF: 0.586

Gnomad4 AMR AF: 0.599

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.654

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.559

Alfa AF: 0.574 Hom.: 15429

Bravo AF: 0.578

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.3
DANN	Benign	0.20

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: rs10404348; hg19: chr19-10840201;