rs11671653

Positions:

• chr19-10727810-G-A
• chr19-10727810-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001005361.3(DNM2):​c.161+9407G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0837 in 152,110 control chromosomes in the GnomAD database, including 564 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 0.084 (564 hom., cov: 32)
• Consequence: DNM2 NM_001005361.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.612

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNM2	NM_001005361.3	c.161+9407G>A		intron_variant		ENST00000389253.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNM2	ENST00000389253.9	c.161+9407G>A		intron_variant		5	NM_001005361.3	A1

Frequencies

GnomAD3 genomes AF: 0.0837 AC: 12718 AN: 151992 Hom.: 564 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0576

Gnomad ASJ AF: 0.0926

Gnomad EAS AF: 0.0458

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.0478

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0816

Gnomad OTH AF: 0.0836

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

GnomAD4 genome AF: 0.0837 AC: 12732 AN: 152110 Hom.: 564 Cov.: 32 AF XY: 0.0804 AC XY: 5980 AN XY: 74352

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.0575

Gnomad4 ASJ AF: 0.0926

Gnomad4 EAS AF: 0.0459

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.0478

Gnomad4 NFE AF: 0.0816

Gnomad4 OTH AF: 0.0832

Alfa AF: 0.0757 Hom.: 575

Bravo AF: 0.0856

Asia WGS AF: 0.0890 AC: 311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	17
DANN	Benign	0.81

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: rs11671653; hg19: chr19-10838486;