Menu
GeneBe

rs11505215

chr7-158926448-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_018051.5(DYNC2I1):c.2418G>T(p.Gly806=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 1,613,322 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0069 ( 12 hom., cov: 33)
Exomes 𝑓: 0.0010 ( 12 hom. )

Consequence

DYNC2I1
NM_018051.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0550
Variant links:
Genes affected
DYNC2I1 (HGNC:21862): (dynein 2 intermediate chain 1) 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) and may facilitate the 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. The encoded protein contains four WD repeats and may play a role in the formation of cilia. Mutations in this gene have been associated with short-rib polydactyly and Jeune syndromes. [provided by RefSeq, Mar 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 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 7-158926448-G-T is Benign according to our data. Variant chr7-158926448-G-T is described in ClinVar as [Benign]. Clinvar id is 474628.Status of the report is criteria_provided_single_submitter, 1 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=-0.055 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0069 (1051/152372) while in subpopulation AFR AF= 0.0223 (927/41576). AF 95% confidence interval is 0.0211. There are 12 homozygotes in gnomad4. There are 498 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 12 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DYNC2I1NM_018051.5 linkuse as main transcriptc.2418G>T p.Gly806= synonymous_variant 19/25 ENST00000407559.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DYNC2I1ENST00000407559.8 linkuse as main transcriptc.2418G>T p.Gly806= synonymous_variant 19/251 NM_018051.5 P1
DYNC2I1ENST00000444851.5 linkuse as main transcriptc.*7G>T 3_prime_UTR_variant, NMD_transcript_variant 14/201
DYNC2I1ENST00000467220.1 linkuse as main transcriptn.4217G>T non_coding_transcript_exon_variant 14/202

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00686
AC:
1045
AN:
152254
Hom.:
12
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0222
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00536
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000456
Gnomad OTH
AF:
0.00430
GnomAD3 exomes
AF:
0.00187
AC:
463
AN:
247528
Hom.:
1
AF XY:
0.00156
AC XY:
209
AN XY:
134266
show subpopulations
Gnomad AFR exome
AF:
0.0232
Gnomad AMR exome
AF:
0.00166
Gnomad ASJ exome
AF:
0.000399
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000659
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000321
Gnomad OTH exome
AF:
0.00133
GnomAD4 exome
AF:
0.00100
AC:
1462
AN:
1460950
Hom.:
12
Cov.:
35
AF XY:
0.000885
AC XY:
643
AN XY:
726666
show subpopulations
Gnomad4 AFR exome
AF:
0.0247
Gnomad4 AMR exome
AF:
0.00195
Gnomad4 ASJ exome
AF:
0.000498
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000465
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000376
Gnomad4 OTH exome
AF:
0.00162
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00690
AC:
1051
AN:
152372
Hom.:
12
Cov.:
33
AF XY:
0.00668
AC XY:
498
AN XY:
74518
show subpopulations
Gnomad4 AFR
AF:
0.0223
Gnomad4 AMR
AF:
0.00536
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000456
Gnomad4 OTH
AF:
0.00426
Alfa
AF:
0.00403
Hom.:
10
Bravo
AF:
0.00732
Asia WGS
AF:
0.00289
AC:
10
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Short-rib thoracic dysplasia 8 with or without polydactyly Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 24, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.40
Cadd
Benign
2.5
Dann
Benign
0.70
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.17
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: rs11505215; hg19: chr7-158719139; API