Variant 7-158926304-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018051.5(DYNC2I1):c.2371+4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00928 in 1,608,350 control chromosomes in the GnomAD database, including 653 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 213 hom., cov: 34)

Exomes 𝑓: 0.0071 ( 440 hom. )

Consequence

DYNC2I1
NM_018051.5 splice_region, intron

Scores

Splicing: ADA: 0.0001356

Clinical Significance

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

Conservation

PhyloP100: -2.43

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]

DYNC2I1 links:

DYNC2I1 (HGNC:):

DYNC2I1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 7-158926304-C-T is Benign according to our data. Variant chr7-158926304-C-T is described in ClinVar as [Benign]. Clinvar id is 474625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNC2I1	NM_018051.5 linkuse as main transcript	c.2371+4C>T		splice_region_variant, intron_variant		ENST00000407559.8	NP_060521.4	Q8WVS4A0A140VK66

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
DYNC2I1	ENST00000407559.8 linkuse as main transcript	c.2371+4C>T	splice_region_variant, intron_variant	1	NM_018051.5	ENSP00000384290.3	Q8WVS4
DYNC2I1	ENST00000444851.5 linkuse as main transcript	n.1529+4C>T	splice_region_variant, intron_variant	1		ENSP00000392608.1	H7C022
DYNC2I1	ENST00000467220.1 linkuse as main transcript	n.4170+4C>T	splice_region_variant, intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0297

AC:

4519

AN:

152204

Hom.:

212

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0844

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0104

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.130

Gnomad SAS

AF:

0.0257

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.0215

GnomAD3 exomes

AF:

0.0180

AC:

4277

AN:

237074

Hom.:

198

AF XY:

0.0166

AC XY:

2124

AN XY:

128312

show subpopulations

Gnomad AFR exome

AF:

0.0835

Gnomad AMR exome

AF:

0.00332

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.133

Gnomad SAS exome

AF:

0.0216

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000244

Gnomad OTH exome

AF:

0.00707

GnomAD4 exome

AF:

0.00714

AC:

10389

AN:

1456028

Hom.:

440

Cov.:

AF XY:

0.00714

AC XY:

5169

AN XY:

723798

show subpopulations

Gnomad4 AFR exome

AF:

0.0833

Gnomad4 AMR exome

AF:

0.00368

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.120

Gnomad4 SAS exome

AF:

0.0212

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000115

Gnomad4 OTH exome

AF:

0.0126

GnomAD4 genome

AF:

0.0297

AC:

4530

AN:

152322

Hom.:

213

Cov.:

AF XY:

0.0304

AC XY:

2264

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0842

Gnomad4 AMR

AF:

0.0104

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.130

Gnomad4 SAS

AF:

0.0263

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.0232

Alfa

AF:

0.0109

Hom.:

Bravo

AF:

0.0323

Asia WGS

AF:

0.0600

AC:

208

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Short-rib thoracic dysplasia 8 with or without polydactyly

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 28, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.055

DANN

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00014

dbscSNV1_RF

Benign

0.012

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over