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GeneBe

rs75450756

chr9-128635116-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_052844.4(DYNC2I2):c.957G>A(p.Leu319=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00487 in 1,612,520 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0058 ( 24 hom., cov: 33)
Exomes 𝑓: 0.0048 ( 120 hom. )

Consequence

DYNC2I2
NM_052844.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.854
Variant links:
Genes affected
DYNC2I2 (HGNC:28296): (dynein 2 intermediate chain 2) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. Defects in this gene are a cause of short-rib thoracic dysplasia 11 with or without polydactyly. [provided by RefSeq, Mar 2014]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 9-128635116-C-T is Benign according to our data. Variant chr9-128635116-C-T is described in ClinVar as [Benign]. Clinvar id is 474851.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.854 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.057 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DYNC2I2NM_052844.4 linkuse as main transcriptc.957G>A p.Leu319= synonymous_variant 6/9 ENST00000372715.7
DYNC2I2XM_047424057.1 linkuse as main transcriptc.957G>A p.Leu319= synonymous_variant 7/10
DYNC2I2XM_011519179.3 linkuse as main transcriptc.873G>A p.Leu291= synonymous_variant 7/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DYNC2I2ENST00000372715.7 linkuse as main transcriptc.957G>A p.Leu319= synonymous_variant 6/91 NM_052844.4 P1
DYNC2I2ENST00000483181.1 linkuse as main transcriptn.550G>A non_coding_transcript_exon_variant 2/32

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00581
AC:
885
AN:
152218
Hom.:
24
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000434
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00327
Gnomad ASJ
AF:
0.00461
Gnomad EAS
AF:
0.0627
Gnomad SAS
AF:
0.00310
Gnomad FIN
AF:
0.0329
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00147
Gnomad OTH
AF:
0.00478
GnomAD3 exomes
AF:
0.0111
AC:
2764
AN:
249500
Hom.:
57
AF XY:
0.0102
AC XY:
1384
AN XY:
135038
show subpopulations
Gnomad AFR exome
AF:
0.000494
Gnomad AMR exome
AF:
0.00879
Gnomad ASJ exome
AF:
0.00621
Gnomad EAS exome
AF:
0.0691
Gnomad SAS exome
AF:
0.00472
Gnomad FIN exome
AF:
0.0339
Gnomad NFE exome
AF:
0.00174
Gnomad OTH exome
AF:
0.00854
GnomAD4 exome
AF:
0.00477
AC:
6972
AN:
1460184
Hom.:
120
Cov.:
33
AF XY:
0.00471
AC XY:
3419
AN XY:
726300
show subpopulations
Gnomad4 AFR exome
AF:
0.000299
Gnomad4 AMR exome
AF:
0.00751
Gnomad4 ASJ exome
AF:
0.00602
Gnomad4 EAS exome
AF:
0.0633
Gnomad4 SAS exome
AF:
0.00450
Gnomad4 FIN exome
AF:
0.0295
Gnomad4 NFE exome
AF:
0.00145
Gnomad4 OTH exome
AF:
0.00653
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00578
AC:
881
AN:
152336
Hom.:
24
Cov.:
33
AF XY:
0.00722
AC XY:
538
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.000433
Gnomad4 AMR
AF:
0.00320
Gnomad4 ASJ
AF:
0.00461
Gnomad4 EAS
AF:
0.0626
Gnomad4 SAS
AF:
0.00248
Gnomad4 FIN
AF:
0.0329
Gnomad4 NFE
AF:
0.00147
Gnomad4 OTH
AF:
0.00520
Alfa
AF:
0.00206
Hom.:
0
Bravo
AF:
0.00459
Asia WGS
AF:
0.0220
AC:
77
AN:
3478
EpiCase
AF:
0.000763
EpiControl
AF:
0.00125

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Short-rib thoracic dysplasia 11 with or without polydactyly Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJul 09, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.40
Cadd
Benign
7.7
Dann
Benign
0.88

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs75450756; hg19: chr9-131397395; API