GeneBe

rs746910264

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001378.3(DYNC1I2):​c.512-9_512-4delTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000127 in 789,106 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 16)
Exomes 𝑓: 0.0000013 ( 0 hom. )

Consequence

DYNC1I2
NM_001378.3 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.970

Publications

0 publications found
Variant links:
Genes affected
DYNC1I2 (HGNC:2964): (dynein cytoplasmic 1 intermediate chain 2) This gene encodes a member of the dynein intermediate chain family. The encoded protein is a non-catalytic component of the cytoplasmic dynein 1 complex, which acts as a retrograde microtubule motor to transport organelles and vesicles. A pseudogene of this gene is located on chromosome 10. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]
DYNC1I2 Gene-Disease associations (from GenCC):
  • neurodevelopmental disorder with microcephaly and structural brain anomalies
    Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DYNC1I2NM_001378.3 linkc.512-9_512-4delTTTTTT splice_region_variant, intron_variant Intron 7 of 17 ENST00000397119.8 NP_001369.1 Q13409-1A0A140VKE9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DYNC1I2ENST00000397119.8 linkc.512-19_512-14delTTTTTT intron_variant Intron 7 of 17 1 NM_001378.3 ENSP00000380308.3 Q13409-1

Frequencies

GnomAD3 genomes
Cov.:
16
GnomAD4 exome
AF:
0.00000127
AC:
1
AN:
789106
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
398806
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
15682
American (AMR)
AF:
0.00
AC:
0
AN:
15278
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
15038
East Asian (EAS)
AF:
0.00
AC:
0
AN:
25444
South Asian (SAS)
AF:
0.00
AC:
0
AN:
39548
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
36242
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2308
European-Non Finnish (NFE)
AF:
0.00000165
AC:
1
AN:
605446
Other (OTH)
AF:
0.00
AC:
0
AN:
34120
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
16

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.97

Splicing

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

Publications

Other links and lift over

dbSNP: rs746910264; hg19: chr2-172582108; API