2-171725598-GTT-G

Position:

• chr2-171725598-GTT-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6

The NM_001378.3(DYNC1I2):​c.512-5_512-4delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00346 in 885,564 control chromosomes in the GnomAD database, including 2 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 0.00094 (1 hom., cov: 22)
  • Exomes 𝑓: 0.0038 (1 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 Likely_benign. Variant got -1 ACMG points.

• BP6: Variant 2-171725598-GTT-G is Benign according to our data. Variant chr2-171725598-GTT-G is described in ClinVar as [Benign]. Clinvar id is 3056393.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNC1I2	NM_001378.3	c.512-5_512-4delTT		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.512-5_512-4delTT		splice_region_variant, intron_variant		1	NM_001378.3	ENSP00000380308.3

Frequencies

GnomAD3 genomes AF: 0.000933 AC: 99 AN: 106072 Hom.: 1 Cov.: 22

Gnomad AFR AF: 0.000578

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00102

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0181

Gnomad SAS AF: 0.000866

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000198

Gnomad OTH AF: 0.00138

GnomAD4 exome AF: 0.00380 AC: 2962 AN: 779480 Hom.: 1 AF XY: 0.00383 AC XY: 1509 AN XY: 393814

Gnomad4 AFR exome AF: 0.00342

Gnomad4 AMR exome AF: 0.00662

Gnomad4 ASJ exome AF: 0.00263

Gnomad4 EAS exome AF: 0.0101

Gnomad4 SAS exome AF: 0.00408

Gnomad4 FIN exome AF: 0.00241

Gnomad4 NFE exome AF: 0.00353

Gnomad4 OTH exome AF: 0.00446

GnomAD4 genome AF: 0.000943 AC: 100 AN: 106084 Hom.: 1 Cov.: 22 AF XY: 0.000786 AC XY: 40 AN XY: 50862

Gnomad4 AFR AF: 0.000577

Gnomad4 AMR AF: 0.00102

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0181

Gnomad4 SAS AF: 0.000869

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000397

Gnomad4 OTH AF: 0.00137

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

Nov 19, 2019

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)		0.010		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;