11-30878716-TAAAAAA-TAAA

Variant names:

• chr11-30878716-TAAA-T
• rs5790842
• NM_001387274.1:c.5234-8_5234-6delTTT

Variant summary

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

The NM_001387274.1(DCDC1):​c.5234-8_5234-6delTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0051 in 1,374,522 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 0.00016 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0057 (0 hom.)
• Consequence: DCDC1 NM_001387274.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 1 publications found

Genes affected

DCDC1 (HGNC:20625): (doublecortin domain containing 1) This gene encodes a member of the doublecortin family. The protein encoded by this gene is a hydrophilic, intracellular protein. It contains a single doublecortin domain and is unable to bind microtubules and to regulate microtubule polymerization. This gene is mainly expressed in adult testis. It does not have a mouse homolog. [provided by RefSeq, Sep 2010]

ENSG00000287373 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Variant has high frequency in the SAS (0.0126) population. However there is too low homozygotes in high coverage region: (expected more than 8, got 0).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387274.1. 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
	DCDC1	NM_001387274.1	MANE Select	c.5234-8_5234-6delTTT		splice_region intron	N/A	NP_001374203.1	A0A804HJA9
	DCDC1	NM_001367979.1		c.5225-8_5225-6delTTT		splice_region intron	N/A	NP_001354908.1	M0R2J8-1
	DCDC1	NM_020869.4		c.2546-8_2546-6delTTT		splice_region intron	N/A	NP_065920.2	B6ZDN3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCDC1	ENST00000684477.1	MANE Select	c.5234-8_5234-6delTTT		splice_region intron	N/A	ENSP00000507427.1	A0A804HJA9
	DCDC1	ENST00000597505.5	TSL:5	c.5225-8_5225-6delTTT		splice_region intron	N/A	ENSP00000472625.1	M0R2J8-1
	DCDC1	ENST00000406071.6	TSL:5	c.2546-8_2546-6delTTT		splice_region intron	N/A	ENSP00000385936.3	B6ZDN3

Frequencies

GnomAD3 genomes AF: 0.000157 AC: 22 AN: 140166 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000161

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000143

Gnomad ASJ AF: 0.000296

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000364

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000154

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0104 AC: 1188 AN: 114698 AF XY: 0.0110

Gnomad AFR exome AF: 0.00599

Gnomad AMR exome AF: 0.0121

Gnomad ASJ exome AF: 0.0219

Gnomad EAS exome AF: 0.00730

Gnomad FIN exome AF: 0.00329

Gnomad NFE exome AF: 0.0100

Gnomad OTH exome AF: 0.0187

GnomAD4 exome AF: 0.00566 AC: 6986 AN: 1234356 Hom.: 0 AF XY: 0.00614 AC XY: 3759 AN XY: 611984

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

African (AFR) AF: 0.00603 AC: 158 AN: 26182

American (AMR) AF: 0.0107 AC: 253 AN: 23708

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 200 AN: 19152

East Asian (EAS) AF: 0.00361 AC: 121 AN: 33548

South Asian (SAS) AF: 0.0133 AC: 863 AN: 64762

European-Finnish (FIN) AF: 0.00583 AC: 237 AN: 40618

Middle Eastern (MID) AF: 0.00370 AC: 16 AN: 4330

European-Non Finnish (NFE) AF: 0.00497 AC: 4823 AN: 971344

Other (OTH) AF: 0.00621 AC: 315 AN: 50712

⚠️ 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 AF: 0.000157 AC: 22 AN: 140166 Hom.: 0 Cov.: 0 AF XY: 0.000192 AC XY: 13 AN XY: 67774

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

African (AFR) AF: 0.000161 AC: 6 AN: 37308

American (AMR) AF: 0.000143 AC: 2 AN: 13966

Ashkenazi Jewish (ASJ) AF: 0.000296 AC: 1 AN: 3380

East Asian (EAS) AF: 0.00 AC: 0 AN: 4768

South Asian (SAS) AF: 0.00 AC: 0 AN: 4378

European-Finnish (FIN) AF: 0.000364 AC: 3 AN: 8238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 296

European-Non Finnish (NFE) AF: 0.000154 AC: 10 AN: 65058

Other (OTH) AF: 0.00 AC: 0 AN: 1898

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000000433867), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 578

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=94/6	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs5790842; hg19: chr11-30900263;