rs897409469

Variant names:

• chr9-128250833-G-A
• rs897409469
• NM_004408.4:c.2427G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-128250833-G-A
• chr9-128250833-G-C
• chr9-128250833-G-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_004408.4(DNM1):​c.2427G>A​(p.Leu809Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000868 in 1,151,630 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L809L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.7e-7 (0 hom.)
• Consequence: DNM1 NM_004408.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.53
• Publications: 0 publications found

Genes affected

DNM1 (HGNC:2972): (dynamin 1) This gene encodes a member of the dynamin subfamily of GTP-binding proteins. The encoded protein possesses unique mechanochemical properties used to tubulate and sever membranes, and is involved in clathrin-mediated endocytosis and other vesicular trafficking processes. Actin and other cytoskeletal proteins act as binding partners for the encoded protein, which can also self-assemble leading to stimulation of GTPase activity. More than sixty highly conserved copies of the 3' region of this gene are found elsewhere in the genome, particularly on chromosomes Y and 15. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

DNM1 Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• developmental and epileptic encephalopathy, 31A

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• developmental and epileptic encephalopathy, 31B

  Inheritance: AR, AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• Lennox-Gastaut syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=2.53 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004408.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNM1	NM_004408.4	MANE Select	c.2427G>A	p.Leu809Leu	synonymous	Exon 21 of 22	NP_004399.2
	DNM1	NM_001374269.1		c.2427G>A	p.Leu809Leu	synonymous	Exon 21 of 22	NP_001361198.1
	DNM1	NM_001288739.2		c.2427G>A	p.Leu809Leu	synonymous	Exon 21 of 22	NP_001275668.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNM1	ENST00000372923.8	TSL:1 MANE Select	c.2427G>A	p.Leu809Leu	synonymous	Exon 21 of 22	ENSP00000362014.4
	DNM1	ENST00000486160.3	TSL:1	c.2427G>A	p.Leu809Leu	synonymous	Exon 21 of 22	ENSP00000420045.1
	DNM1	ENST00000634267.2	TSL:5	c.2427G>A	p.Leu809Leu	synonymous	Exon 21 of 22	ENSP00000489096.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.68e-7 AC: 1 AN: 1151630 Hom.: 0 Cov.: 31 AF XY: 0.00000181 AC XY: 1 AN XY: 553774

African (AFR) AF: 0.00 AC: 0 AN: 23146

American (AMR) AF: 0.00 AC: 0 AN: 8806

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15448

East Asian (EAS) AF: 0.00 AC: 0 AN: 27056

South Asian (SAS) AF: 0.00 AC: 0 AN: 35372

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3258

European-Non Finnish (NFE) AF: 0.00000104 AC: 1 AN: 965798

Other (OTH) AF: 0.00 AC: 0 AN: 47116

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	9.3
DANN	Benign	0.89
PhyloP100		2.5
PromoterAI		-0.040	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs897409469; hg19: chr9-131013112;