chr19-10718224-G-C

Variant names:

• chr19-10718224-G-C
• rs753599004
• NM_001005361.3:c.-19G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001005361.3(DNM2):​c.-19G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,462,502 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.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: DNM2 NM_001005361.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.334
• Publications: 0 publications found

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]

MIR638 (HGNC:32894): (microRNA 638) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNM2	NM_001005361.3	c.-19G>C		5_prime_UTR_variant	Exon 1 of 21	ENST00000389253.9	NP_001005361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNM2	ENST00000389253.9	c.-19G>C		5_prime_UTR_variant	Exon 1 of 21	5	NM_001005361.3	ENSP00000373905.4

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152076 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000831 AC: 7 AN: 84260 AF XY: 0.0000838

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000249

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000132 AC: 173 AN: 1310426 Hom.: 0 Cov.: 30 AF XY: 0.000110 AC XY: 71 AN XY: 646026

African (AFR) AF: 0.000152 AC: 4 AN: 26402

American (AMR) AF: 0.00 AC: 0 AN: 26026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22606

East Asian (EAS) AF: 0.00 AC: 0 AN: 27290

South Asian (SAS) AF: 0.00 AC: 0 AN: 70820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43246

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3816

European-Non Finnish (NFE) AF: 0.000161 AC: 167 AN: 1036710

Other (OTH) AF: 0.0000374 AC: 2 AN: 53510

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152076 Hom.: 0 Cov.: 33 AF XY: 0.0000942 AC XY: 7 AN XY: 74300

African (AFR) AF: 0.0000724 AC: 3 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 67990

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000945

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Benign	0.89
PhyloP100		0.33
PromoterAI		0.036	Neutral

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: rs753599004; hg19: chr19-10828900;