rs2421992

Variant names:

• chr1-172272111-C-T
• rs2421992
• NM_015569.5:c.1769+18429C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015569.5(DNM3):​c.1769+18429C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 151,822 control chromosomes in the GnomAD database, including 30,515 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 0.63 (30515 hom., cov: 32)
• Consequence: DNM3 NM_015569.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.636
• Publications: 16 publications found

Genes affected

DNM3 (HGNC:29125): (dynamin 3) This gene encodes a member of a family of guanosine triphosphate (GTP)-binding proteins that associate with microtubules and are involved in vesicular transport. The encoded protein functions in the development of megakaryocytes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNM3	NM_015569.5	c.1769+18429C>T		intron_variant	Intron 15 of 20	ENST00000627582.3	NP_056384.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNM3	ENST00000627582.3	c.1769+18429C>T		intron_variant	Intron 15 of 20	1	NM_015569.5	ENSP00000486701.1

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94888 AN: 151706 Hom.: 30485 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.625 AC: 94961 AN: 151822 Hom.: 30515 Cov.: 32 AF XY: 0.627 AC XY: 46559 AN XY: 74202

African (AFR) AF: 0.473 AC: 19595 AN: 41388

American (AMR) AF: 0.694 AC: 10563 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.606 AC: 2098 AN: 3464

East Asian (EAS) AF: 0.688 AC: 3554 AN: 5166

South Asian (SAS) AF: 0.526 AC: 2530 AN: 4810

European-Finnish (FIN) AF: 0.734 AC: 7743 AN: 10556

Middle Eastern (MID) AF: 0.507 AC: 148 AN: 292

European-Non Finnish (NFE) AF: 0.690 AC: 46824 AN: 67904

Other (OTH) AF: 0.605 AC: 1272 AN: 2104

Alfa AF: 0.676 Hom.: 106075

Bravo AF: 0.619

Asia WGS AF: 0.578 AC: 2005 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.5
DANN	Benign	0.88
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2421992; hg19: chr1-172241251;