Variant 7-158869740-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_018051.5(DYNC2I1):c.16-115C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0109 in 730,332 control chromosomes in the GnomAD database, including 132 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.018 ( 51 hom., cov: 33)

Exomes 𝑓: 0.0089 ( 81 hom. )

Consequence

DYNC2I1
NM_018051.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.03

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 7-158869740-C-T is Benign according to our data. Variant chr7-158869740-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1706664.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0184 (2799/152234) while in subpopulation AFR AF= 0.0398 (1652/41514). AF 95% confidence interval is 0.0382. There are 51 homozygotes in gnomad4. There are 1310 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 51 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNC2I1	NM_018051.5 linkuse as main transcript	c.16-115C>T		intron_variant		ENST00000407559.8	NP_060521.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYNC2I1	ENST00000407559.8 linkuse as main transcript	c.16-115C>T		intron_variant		1	NM_018051.5	ENSP00000384290	P1
DYNC2I1	ENST00000397143.3 linkuse as main transcript	c.-123-115C>T		intron_variant		3		ENSP00000380330

Frequencies

GnomAD3 genomes

AF:

0.0184

AC:

2794

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0398

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0232

Gnomad ASJ

AF:

0.0582

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.00712

Gnomad OTH

AF:

0.0292

GnomAD4 exome

AF:

0.00891

AC:

5152

AN:

578098

Hom.:

AF XY:

0.00895

AC XY:

2682

AN XY:

299714

show subpopulations

Gnomad4 AFR exome

AF:

0.0446

Gnomad4 AMR exome

AF:

0.0162

Gnomad4 ASJ exome

AF:

0.0592

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00392

Gnomad4 FIN exome

AF:

0.000136

Gnomad4 NFE exome

AF:

0.00666

Gnomad4 OTH exome

AF:

0.0172

GnomAD4 genome

AF:

0.0184

AC:

2799

AN:

152234

Hom.:

Cov.:

AF XY:

0.0176

AC XY:

1310

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0398

Gnomad4 AMR

AF:

0.0231

Gnomad4 ASJ

AF:

0.0582

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00712

Gnomad4 OTH

AF:

0.0289

Alfa

AF:

0.0154

Hom.:

Bravo

AF:

0.0221

Asia WGS

AF:

0.00260

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 19, 2021

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

3.0

DANN

Benign

0.80

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.

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