2-171725615-C-A

Position:

• chr2-171725615-C-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_001378.3(DYNC1I2):​c.512-3C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 18)
  • Exomes 𝑓: 0.013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DYNC1I2 NM_001378.3 splice_region, intron
• Scores: Splicing: ADA: 0.1218
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.24

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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 2-171725615-C-A is Benign according to our data. Variant chr2-171725615-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3055403.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.512-3C>A		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.512-3C>A		splice_region_variant, intron_variant		1	NM_001378.3	ENSP00000380308.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 9 AN: 69564 Hom.: 0 Cov.: 18 FAILED QC

Gnomad AFR AF: 0.0000573

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000707

Gnomad SAS AF: 0.00140

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000895

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0131 AC: 6633 AN: 506604 Hom.: 0 Cov.: 13 AF XY: 0.0125 AC XY: 3174 AN XY: 254724

Gnomad4 AFR exome AF: 0.0130

Gnomad4 AMR exome AF: 0.00229

Gnomad4 ASJ exome AF: 0.00666

Gnomad4 EAS exome AF: 0.00399

Gnomad4 SAS exome AF: 0.00783

Gnomad4 FIN exome AF: 0.00235

Gnomad4 NFE exome AF: 0.0153

Gnomad4 OTH exome AF: 0.0113

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000129 AC: 9 AN: 69592 Hom.: 0 Cov.: 18 AF XY: 0.000152 AC XY: 5 AN XY: 32798

Gnomad4 AFR AF: 0.0000572

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000709

Gnomad4 SAS AF: 0.00140

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000896

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

DYNC1I2-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 06, 2019

This variant is classified as likely 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

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	13
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.12
dbscSNV1_RF	Benign	0.39
SpliceAI score (max)		0.090		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: rs756992961; hg19: chr2-172582125;