NM_001135556.2:c.223+189dupG

Variant names:

• chr7-95810694-A-AG
• rs35308603
• NM_001135556.2:c.223+189dupG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001135556.2(DYNC1I1):​c.223+189dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.65 (32521 hom., cov: 0)
• Consequence: DYNC1I1 NM_001135556.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.35
• Publications: 0 publications found

Genes affected

DYNC1I1 (HGNC:2963): (dynein cytoplasmic 1 intermediate chain 1) Enables spectrin binding activity. Involved in vesicle transport along microtubule. Located in several cellular components, including kinetochore; recycling endosome; and spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 7-95810694-A-AG is Benign according to our data. Variant chr7-95810694-A-AG is described in ClinVar as Benign. ClinVar VariationId is 1224657.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135556.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC1I1	NM_001135556.2	MANE Select	c.223+189dupG		intron	N/A	NP_001129028.1	O14576-2
	DYNC1I1	NM_004411.5		c.223+189dupG		intron	N/A	NP_004402.1	O14576-1
	DYNC1I1	NM_001278421.2		c.223+189dupG		intron	N/A	NP_001265350.1	O14576-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC1I1	ENST00000447467.6	TSL:1 MANE Select	c.223+188_223+189insG		intron	N/A	ENSP00000392337.2	O14576-2
	DYNC1I1	ENST00000324972.10	TSL:1	c.223+188_223+189insG		intron	N/A	ENSP00000320130.6	O14576-1
	DYNC1I1	ENST00000457059.2	TSL:1	c.223+188_223+189insG		intron	N/A	ENSP00000412444.1	O14576-2

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98053 AN: 151816 Hom.: 32461 Cov.: 0

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.731

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.601

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.646 AC: 98180 AN: 151934 Hom.: 32521 Cov.: 0 AF XY: 0.651 AC XY: 48308 AN XY: 74238

African (AFR) AF: 0.789 AC: 32715 AN: 41460

American (AMR) AF: 0.669 AC: 10190 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1857 AN: 3470

East Asian (EAS) AF: 0.731 AC: 3777 AN: 5168

South Asian (SAS) AF: 0.607 AC: 2919 AN: 4812

European-Finnish (FIN) AF: 0.659 AC: 6959 AN: 10552

Middle Eastern (MID) AF: 0.497 AC: 144 AN: 290

European-Non Finnish (NFE) AF: 0.557 AC: 37857 AN: 67924

Other (OTH) AF: 0.607 AC: 1281 AN: 2110

Alfa AF: 0.547 Hom.: 2859

Asia WGS AF: 0.702 AC: 2437 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs35308603; hg19: chr7-95440006;