7-95813093-CTTTTT-CTTTTTTTTTTTTTT

Variant names:

• chr7-95813093-C-CTTTTTTTTT
• rs11452827
• NM_001135556.2:c.224-148_224-140dupTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001135556.2(DYNC1I1):​c.224-148_224-140dupTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000808 in 1,114,300 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000072 (0 hom.)
• Consequence: DYNC1I1 NM_001135556.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.361
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.224-148_224-140dupTTTTTTTTT		intron	N/A	NP_001129028.1	O14576-2
	DYNC1I1	NM_004411.5		c.224-97_224-89dupTTTTTTTTT		intron	N/A	NP_004402.1	O14576-1
	DYNC1I1	NM_001278421.2		c.224-97_224-89dupTTTTTTTTT		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.224-154_224-153insTTTTTTTTT		intron	N/A	ENSP00000392337.2	O14576-2
	DYNC1I1	ENST00000324972.10	TSL:1	c.224-103_224-102insTTTTTTTTT		intron	N/A	ENSP00000320130.6	O14576-1
	DYNC1I1	ENST00000457059.2	TSL:1	c.224-154_224-153insTTTTTTTTT		intron	N/A	ENSP00000412444.1	O14576-2

Frequencies

GnomAD3 genomes AF: 0.0000142 AC: 2 AN: 140376 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000296

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000153

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000719 AC: 7 AN: 973924 Hom.: 0 AF XY: 0.0000103 AC XY: 5 AN XY: 484630

African (AFR) AF: 0.00 AC: 0 AN: 18796

American (AMR) AF: 0.00 AC: 0 AN: 17456

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16878

East Asian (EAS) AF: 0.0000377 AC: 1 AN: 26528

South Asian (SAS) AF: 0.0000203 AC: 1 AN: 49362

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2948

European-Non Finnish (NFE) AF: 0.00000648 AC: 5 AN: 771072

Other (OTH) AF: 0.00 AC: 0 AN: 40412

GnomAD4 genome AF: 0.0000142 AC: 2 AN: 140376 Hom.: 0 Cov.: 0 AF XY: 0.0000148 AC XY: 1 AN XY: 67556

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 38112

American (AMR) AF: 0.00 AC: 0 AN: 13880

Ashkenazi Jewish (ASJ) AF: 0.000296 AC: 1 AN: 3384

East Asian (EAS) AF: 0.00 AC: 0 AN: 4846

South Asian (SAS) AF: 0.00 AC: 0 AN: 4522

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7086

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000153 AC: 1 AN: 65436

Other (OTH) AF: 0.00 AC: 0 AN: 1924

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0296732), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00179 Hom.: 272

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.36

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11452827; hg19: chr7-95442405;