rs199742926

chr19-10795332-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001005361.3(DNM2):c.1129-40C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00564 in 1,611,006 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0059 (38 hom.)
• Consequence: DNM2 NM_001005361.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.118

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=-0.87).
• BP6: Variant 19-10795332-C-T is Benign according to our data. Variant chr19-10795332-C-T is described in ClinVar as [Benign]. Clinvar id is 256863.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00362 (551/152334) while in subpopulation NFE AF= 0.00623 (424/68028). AF 95% confidence interval is 0.00574. There are 3 homozygotes in gnomad4. There are 246 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNM2	NM_001005361.3	c.1129-40C>T		intron_variant		ENST00000389253.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNM2	ENST00000389253.9	c.1129-40C>T		intron_variant		5	NM_001005361.3	A1

Frequencies

GnomAD3 genomes AF: 0.00362 AC: 551 AN: 152216 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00132

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00623

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00331 AC: 831 AN: 251238 Hom.: 2 AF XY: 0.00328 AC XY: 445 AN XY: 135794

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.00162

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00121

Gnomad FIN exome AF: 0.00243

Gnomad NFE exome AF: 0.00561

Gnomad OTH exome AF: 0.00456

GnomAD4 exome AF: 0.00585 AC: 8536 AN: 1458672 Hom.: 38 Cov.: 30 AF XY: 0.00578 AC XY: 4199 AN XY: 725852

Gnomad4 AFR exome AF: 0.00105

Gnomad4 AMR exome AF: 0.00179

Gnomad4 ASJ exome AF: 0.0000766

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00106

Gnomad4 FIN exome AF: 0.00301

Gnomad4 NFE exome AF: 0.00705

Gnomad4 OTH exome AF: 0.00562

GnomAD4 genome AF: 0.00362 AC: 551 AN: 152334 Hom.: 3 Cov.: 32 AF XY: 0.00330 AC XY: 246 AN XY: 74480

Gnomad4 AFR AF: 0.00123

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00132

Gnomad4 NFE AF: 0.00623

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00433 Hom.: 1

Bravo AF: 0.00380

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	6.3
Dann	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs199742926; hg19: chr19-10906008;