2-171725598-G-GTT

Position:

• chr2-171725598-G-GTT

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_001378.3(DYNC1I2):​c.512-5_512-4dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 889,034 control chromosomes in the GnomAD database, including 64 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 22)
  • Exomes 𝑓: 0.012 (63 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-GTT is Benign according to our data. Variant chr2-171725598-G-GTT is described in ClinVar as [Benign]. Clinvar id is 3056366.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0125 (9773/782970) while in subpopulation SAS AF= 0.0291 (1145/39298). AF 95% confidence interval is 0.0277. There are 63 homozygotes in gnomad4_exome. There are 5362 alleles in male gnomad4_exome subpopulation. Median coverage is 15. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 63 AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00174 AC: 185 AN: 106052 Hom.: 1 Cov.: 22

Gnomad AFR AF: 0.00437

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00120

Gnomad ASJ AF: 0.000376

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000289

Gnomad FIN AF: 0.000392

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000893

Gnomad OTH AF: 0.00138

GnomAD4 exome AF: 0.0125 AC: 9773 AN: 782970 Hom.: 63 Cov.: 15 AF XY: 0.0136 AC XY: 5362 AN XY: 395714

Gnomad4 AFR exome AF: 0.0117

Gnomad4 AMR exome AF: 0.0105

Gnomad4 ASJ exome AF: 0.0196

Gnomad4 EAS exome AF: 0.00400

Gnomad4 SAS exome AF: 0.0291

Gnomad4 FIN exome AF: 0.0157

Gnomad4 NFE exome AF: 0.0114

Gnomad4 OTH exome AF: 0.0138

GnomAD4 genome AF: 0.00174 AC: 185 AN: 106064 Hom.: 1 Cov.: 22 AF XY: 0.00191 AC XY: 97 AN XY: 50850

Gnomad4 AFR AF: 0.00437

Gnomad4 AMR AF: 0.00120

Gnomad4 ASJ AF: 0.000376

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000290

Gnomad4 FIN AF: 0.000392

Gnomad4 NFE AF: 0.000894

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 25, 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

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;