Variant 7-158856606-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.-130C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00457 in 972,698 control chromosomes in the GnomAD database, including 127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0077 ( 37 hom., cov: 35)

Exomes 𝑓: 0.0040 ( 90 hom. )

Consequence

DYNC2I1
NM_018051.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.175

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=-0.87).

BP6

Variant 7-158856606-C-T is Benign according to our data. Variant chr7-158856606-C-T is described in ClinVar as [Benign]. Clinvar id is 1179846.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00767 (1163/151588) while in subpopulation EAS AF= 0.0304 (157/5166). AF 95% confidence interval is 0.0265. There are 37 homozygotes in gnomad4. There are 780 alleles in male gnomad4 subpopulation. Median coverage is 35. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNC2I1	NM_018051.5 link	c.-130C>T		5_prime_UTR_variant	1/25	ENST00000407559.8	NP_060521.4	Q8WVS4A0A140VK66

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYNC2I1	ENST00000407559 link	c.-130C>T		5_prime_UTR_variant	1/25	1	NM_018051.5	ENSP00000384290.3		Q8WVS4

Frequencies

GnomAD3 genomes

AF:

0.00768

AC:

1164

AN:

151470

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00177

Gnomad EAS

AF:

0.0303

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.0779

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00222

Gnomad OTH

AF:

0.00480

GnomAD4 exome

AF:

0.00400

AC:

3284

AN:

821110

Hom.:

Cov.:

AF XY:

0.00388

AC XY:

1527

AN XY:

393586

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000377

Gnomad4 ASJ exome

AF:

0.00153

Gnomad4 EAS exome

AF:

0.0512

Gnomad4 SAS exome

AF:

0.000287

Gnomad4 FIN exome

AF:

0.0724

Gnomad4 NFE exome

AF:

0.000511

Gnomad4 OTH exome

AF:

0.00283

GnomAD4 genome

AF:

0.00767

AC:

1163

AN:

151588

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

780

AN XY:

74148

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00177

Gnomad4 EAS

AF:

0.0304

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.0779

Gnomad4 NFE

AF:

0.00222

Gnomad4 OTH

AF:

0.00475

Alfa

AF:

0.00741

Hom.:

Bravo

AF:

0.00199

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

6.8

DANN

Benign

0.84

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