11-30878716-TAA-T

Variant names:

• chr11-30878716-TAA-T
• rs5790842
• NM_001387274.1:c.5234-7_5234-6delTT

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BA1

The NM_001387274.1(DCDC1):​c.5234-7_5234-6delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,325,020 control chromosomes in the GnomAD database, including 74 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.019 (66 hom., cov: 0)
  • Exomes 𝑓: 0.13 (8 hom.)
• Consequence: DCDC1 NM_001387274.1 splice_region, intron
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.838
• 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: Benign. The variant received -9 ACMG points.

• BP6: Variant 11-30878716-TAA-T is Benign according to our data. Variant chr11-30878716-TAA-T is described in ClinVar as Benign. ClinVar VariationId is 3347052.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0565 is higher than 0.05.

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.5234-7_5234-6delTT		splice_region intron	N/A	NP_001374203.1	A0A804HJA9
	DCDC1	NM_001367979.1		c.5225-7_5225-6delTT		splice_region intron	N/A	NP_001354908.1	M0R2J8-1
	DCDC1	NM_020869.4		c.2546-7_2546-6delTT		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.5234-7_5234-6delTT		splice_region intron	N/A	ENSP00000507427.1	A0A804HJA9
	DCDC1	ENST00000597505.5	TSL:5	c.5225-7_5225-6delTT		splice_region intron	N/A	ENSP00000472625.1	M0R2J8-1
	DCDC1	ENST00000406071.6	TSL:5	c.2546-7_2546-6delTT		splice_region intron	N/A	ENSP00000385936.3	B6ZDN3

Frequencies

GnomAD3 genomes AF: 0.0189 AC: 2642 AN: 140068 Hom.: 65 Cov.: 0

Gnomad AFR AF: 0.0585

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00781

Gnomad ASJ AF: 0.00207

Gnomad EAS AF: 0.000419

Gnomad SAS AF: 0.00183

Gnomad FIN AF: 0.00999

Gnomad MID AF: 0.0136

Gnomad NFE AF: 0.00323

Gnomad OTH AF: 0.0200

GnomAD2 exomes AF: 0.146 AC: 16711 AN: 114698 AF XY: 0.153

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.111

Gnomad ASJ exome AF: 0.212

Gnomad EAS exome AF: 0.0781

Gnomad FIN exome AF: 0.105

Gnomad NFE exome AF: 0.164

Gnomad OTH exome AF: 0.149

GnomAD4 exome AF: 0.125 AC: 148584 AN: 1184910 Hom.: 8 AF XY: 0.129 AC XY: 75617 AN XY: 587788

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

African (AFR) AF: 0.0989 AC: 2519 AN: 25464

American (AMR) AF: 0.114 AC: 2650 AN: 23192

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 3266 AN: 18372

East Asian (EAS) AF: 0.0832 AC: 2690 AN: 32344

South Asian (SAS) AF: 0.149 AC: 9443 AN: 63382

European-Finnish (FIN) AF: 0.121 AC: 4782 AN: 39476

Middle Eastern (MID) AF: 0.111 AC: 464 AN: 4186

European-Non Finnish (NFE) AF: 0.125 AC: 116613 AN: 929712

Other (OTH) AF: 0.126 AC: 6157 AN: 48782

⚠️ 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: 0.0189 AC: 2647 AN: 140110 Hom.: 66 Cov.: 0 AF XY: 0.0183 AC XY: 1240 AN XY: 67780

African (AFR) AF: 0.0586 AC: 2188 AN: 37366

American (AMR) AF: 0.00780 AC: 109 AN: 13976

Ashkenazi Jewish (ASJ) AF: 0.00207 AC: 7 AN: 3378

East Asian (EAS) AF: 0.000421 AC: 2 AN: 4752

South Asian (SAS) AF: 0.00161 AC: 7 AN: 4358

European-Finnish (FIN) AF: 0.00999 AC: 82 AN: 8212

Middle Eastern (MID) AF: 0.0148 AC: 4 AN: 270

European-Non Finnish (NFE) AF: 0.00323 AC: 210 AN: 65012

Other (OTH) AF: 0.0199 AC: 38 AN: 1910

Alfa AF: 0.00 Hom.: 578

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DCDC5-related condition (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.84
Mutation Taster		=98/2	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;