rs75450756

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

short-rib thoracic dysplasia 11 with or without polydactyly
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, G2P
Jeune syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
short rib-polydactyly syndrome, Verma-Naumoff type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

DYNC2I2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DYNC2I2	NM_052844.4 link	c.957G>A	p.Leu319Leu	synonymous_variant	Exon 6 of 9	ENST00000372715.7	NP_443076.2	Q96EX3
DYNC2I2	XM_047424057.1 link	c.957G>A	p.Leu319Leu	synonymous_variant	Exon 7 of 10		XP_047280013.1
DYNC2I2	XM_011519179.3 link	c.873G>A	p.Leu291Leu	synonymous_variant	Exon 7 of 10		XP_011517481.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DYNC2I2	ENST00000372715.7 link	c.957G>A	p.Leu319Leu	synonymous_variant	Exon 6 of 9	1	NM_052844.4	ENSP00000361800.2	Q96EX3
DYNC2I2	ENST00000483181.1 link	n.550G>A		non_coding_transcript_exon_variant	Exon 2 of 3	2
DYNC2I2	ENST00000419989.2 link	n.*382G>A		downstream_gene_variant		5		ENSP00000415421.1	A2A3F8
DYNC2I2	ENST00000473486.1 link	n.*207G>A		downstream_gene_variant		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

GnomAD2 exomes

AF:

0.0111

AC:

2764

AN:

249500

AF XY:

0.0102

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 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

African (AFR)

AF:

0.000299

AC:

AN:

33468

American (AMR)

AF:

0.00751

AC:

335

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.00602

AC:

157

AN:

26078

East Asian (EAS)

AF:

0.0633

AC:

2512

AN:

39680

South Asian (SAS)

AF:

0.00450

AC:

388

AN:

86178

European-Finnish (FIN)

AF:

0.0295

AC:

1555

AN:

52766

Middle Eastern (MID)

AF:

0.000705

AC:

AN:

5676

European-Non Finnish (NFE)

AF:

0.00145

AC:

1617

AN:

1111386

Other (OTH)

AF:

0.00653

AC:

394

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

423

846

1269

1692

2115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00578

AC:

881

AN:

152336

Hom.:

Cov.:

AF XY:

0.00722

AC XY:

538

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.000433

AC:

AN:

41576

American (AMR)

AF:

0.00320

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00461

AC:

AN:

3472

East Asian (EAS)

AF:

0.0626

AC:

324

AN:

5172

South Asian (SAS)

AF:

0.00248

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0329

AC:

350

AN:

10626

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00147

AC:

100

AN:

68028

Other (OTH)

AF:

0.00520

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

143

190

238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Short-rib thoracic dysplasia 11 with or without polydactyly

Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

7.7

(source)

DANN

Benign

0.88

PhyloP100

0.85

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs75450756

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over