chr2-171725598-G-GT

Position:

• chr2-171725598-G-GT

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_001378.3(DYNC1I2):​c.512-4dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 875,940 control chromosomes in the GnomAD database, including 3,314 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.21 (1993 hom., cov: 22)
  • Exomes 𝑓: 0.14 (1321 hom.)
• Consequence: DYNC1I2 NM_001378.3 splice_region, intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.112

Genes affected

DYNC1I2 (HGNC:2964): (dynein cytoplasmic 1 intermediate chain 2) This gene encodes a member of the dynein intermediate chain family. The encoded protein is a non-catalytic component of the cytoplasmic dynein 1 complex, which acts as a retrograde microtubule motor to transport organelles and vesicles. A pseudogene of this gene is located on chromosome 10. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

DYNC1I2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 2-171725598-G-GT is Benign according to our data. Variant chr2-171725598-G-GT is described in ClinVar as [Benign]. Clinvar id is 3060840.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNC1I2	NM_001378.3	c.512-4dupT		splice_region_variant, intron_variant		ENST00000397119.8	NP_001369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYNC1I2	ENST00000397119.8	c.512-4dupT		splice_region_variant, intron_variant		1	NM_001378.3	ENSP00000380308.3

Frequencies

GnomAD3 genomes AF: 0.207 AC: 21894 AN: 105840 Hom.: 1996 Cov.: 22

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.0583

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.233

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.139 AC: 107343 AN: 770090 Hom.: 1321 Cov.: 15 AF XY: 0.142 AC XY: 55121 AN XY: 389146

Gnomad4 AFR exome AF: 0.131

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.195

Gnomad4 EAS exome AF: 0.142

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.183

Gnomad4 NFE exome AF: 0.134

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.207 AC: 21893 AN: 105850 Hom.: 1993 Cov.: 22 AF XY: 0.203 AC XY: 10282 AN XY: 50754

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.0584

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.209

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

DYNC1I2-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 11, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs746910264; hg19: chr2-172582108;