7-95813378-TAAAAA-TA

Variant names:

• chr7-95813378-TAAAA-T
• rs35397709
• NM_001135556.2:c.314+53_314+56delAAAA

Variant summary

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

The NM_001135556.2(DYNC1I1):​c.314+53_314+56delAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000237 in 1,267,860 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: not found (cov: 0)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: DYNC1I1 NM_001135556.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299
• 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.314+53_314+56delAAAA		intron	N/A	NP_001129028.1	O14576-2
	DYNC1I1	NM_004411.5		c.365+53_365+56delAAAA		intron	N/A	NP_004402.1	O14576-1
	DYNC1I1	NM_001278421.2		c.365+53_365+56delAAAA		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.314+42_314+45delAAAA		intron	N/A	ENSP00000392337.2	O14576-2
	DYNC1I1	ENST00000324972.10	TSL:1	c.365+42_365+45delAAAA		intron	N/A	ENSP00000320130.6	O14576-1
	DYNC1I1	ENST00000457059.2	TSL:1	c.314+42_314+45delAAAA		intron	N/A	ENSP00000412444.1	O14576-2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000237 AC: 3 AN: 1267860 Hom.: 0 AF XY: 0.00000478 AC XY: 3 AN XY: 628188

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

African (AFR) AF: 0.00 AC: 0 AN: 27080

American (AMR) AF: 0.00 AC: 0 AN: 24792

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20786

East Asian (EAS) AF: 0.00 AC: 0 AN: 35316

South Asian (SAS) AF: 0.00 AC: 0 AN: 68258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41474

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4900

European-Non Finnish (NFE) AF: 0.00000302 AC: 3 AN: 992712

Other (OTH) AF: 0.00 AC: 0 AN: 52542

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.30

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

Other links and lift over

dbSNP: rs35397709; hg19: chr7-95442690;