rs146077746

chr9-128634895-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_052844.4(DYNC2I2):c.1008C>T(p.Gly336=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,612,834 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (2 hom.)
• Consequence: DYNC2I2 NM_052844.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.58

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 9-128634895-G-A is Benign according to our data. Variant chr9-128634895-G-A is described in ClinVar as [Benign]. Clinvar id is 474843.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DYNC2I2	NM_052844.4	c.1008C>T	p.Gly336=	synonymous_variant	7/9	ENST00000372715.7
DYNC2I2	XM_047424057.1	c.1008C>T	p.Gly336=	synonymous_variant	8/10
DYNC2I2	XM_011519179.3	c.924C>T	p.Gly308=	synonymous_variant	8/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DYNC2I2	ENST00000372715.7	c.1008C>T	p.Gly336=	synonymous_variant	7/9	1	NM_052844.4	P1
DYNC2I2	ENST00000483181.1	n.601C>T		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.00111 AC: 169 AN: 152200 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00367

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00138

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00135 AC: 334 AN: 247386 Hom.: 0 AF XY: 0.00129 AC XY: 174 AN XY: 134646

Gnomad AFR exome AF: 0.0000645

Gnomad AMR exome AF: 0.000698

Gnomad ASJ exome AF: 0.00130

Gnomad EAS exome AF: 0.000165

Gnomad SAS exome AF: 0.0000982

Gnomad FIN exome AF: 0.00450

Gnomad NFE exome AF: 0.00170

Gnomad OTH exome AF: 0.000829

GnomAD4 exome AF: 0.00131 AC: 1907 AN: 1460516 Hom.: 2 Cov.: 33 AF XY: 0.00132 AC XY: 958 AN XY: 726580

Gnomad4 AFR exome AF: 0.000299

Gnomad4 AMR exome AF: 0.000649

Gnomad4 ASJ exome AF: 0.000995

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.00389

Gnomad4 NFE exome AF: 0.00142

Gnomad4 OTH exome AF: 0.000829

GnomAD4 genome AF: 0.00112 AC: 170 AN: 152318 Hom.: 1 Cov.: 33 AF XY: 0.00113 AC XY: 84 AN XY: 74486

Gnomad4 AFR AF: 0.000192

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00367

Gnomad4 NFE AF: 0.00138

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00124 Hom.: 0

Bravo AF: 0.000740

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00142

EpiControl AF: 0.00137

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Short-rib thoracic dysplasia 11 with or without polydactyly Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 20, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	0.19
Dann	Benign	0.90
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.29		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.29		Position offset: 6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs146077746; hg19: chr9-131397174; COSMIC: COSV100823699; COSMIC: COSV100823699;