Variant rs75450756 details in Genebe, Genetics Data Aggregator

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.Leu319Leu) 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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

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]

DYNC2I2 links:

DYNC2I2 (HGNC:):

DYNC2I2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

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

Synonymous conserved (PhyloP=0.854 with no splicing effect.

BA1

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	Protein	UniProt
DYNC2I2	NM_052844.4 linkuse as main transcript	c.957G>A	p.Leu319Leu	synonymous_variant	6/9	ENST00000372715.7	NP_443076.2	Q96EX3
DYNC2I2	XM_047424057.1 linkuse as main transcript	c.957G>A	p.Leu319Leu	synonymous_variant	7/10		XP_047280013.1
DYNC2I2	XM_011519179.3 linkuse as main transcript	c.873G>A	p.Leu291Leu	synonymous_variant	7/10		XP_011517481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYNC2I2	ENST00000372715.7 linkuse as main transcript	c.957G>A	p.Leu319Leu	synonymous_variant	6/9	1	NM_052844.4	ENSP00000361800.2		Q96EX3
DYNC2I2	ENST00000483181.1 linkuse as main transcript	n.550G>A		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

AF:

0.00581

AC:

885

AN:

152218

Hom.:

Cov.:

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.:

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.:

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

AF:

0.00578

AC:

881

AN:

152336

Hom.:

Cov.:

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.:

Bravo

AF:

0.00459

Asia WGS

AF:

0.0220

AC:

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.00125

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

Short-rib thoracic dysplasia 11 with or without polydactyly

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

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.

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