11-30881290-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001387274.1(DCDC1):c.5101T>C(p.Ser1701Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,613,262 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. 7/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (33 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (33 hom.)
• Consequence: DCDC1 NM_001387274.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0590

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]

LOC124902656 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009404242).
• BP6: Variant 11-30881290-A-G is Benign according to our data. Variant chr11-30881290-A-G is described in ClinVar as [Benign]. Clinvar id is 718774.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0104 (1580/152252) while in subpopulation AFR AF= 0.0361 (1498/41542). AF 95% confidence interval is 0.0345. There are 33 homozygotes in gnomad4. There are 736 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCDC1	NM_001387274.1	c.5101T>C	p.Ser1701Pro	missense_variant	37/39	ENST00000684477.1
LOC124902656	XR_007062643.1	n.494-5165A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCDC1	ENST00000684477.1	c.5101T>C	p.Ser1701Pro	missense_variant	37/39		NM_001387274.1	A2

Frequencies

GnomAD3 genomes AF: 0.0104 AC: 1581 AN: 152134 Hom.: 33 Cov.: 33

Gnomad AFR AF: 0.0362

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00301

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00955

GnomAD3 exomes AF: 0.00257 AC: 631 AN: 246000 Hom.: 11 AF XY: 0.00190 AC XY: 254 AN XY: 133642

Gnomad AFR exome AF: 0.0340

Gnomad AMR exome AF: 0.00174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000291

Gnomad OTH exome AF: 0.00200

GnomAD4 exome AF: 0.00115 AC: 1674 AN: 1461010 Hom.: 33 Cov.: 30 AF XY: 0.000969 AC XY: 704 AN XY: 726790

Gnomad4 AFR exome AF: 0.0359

Gnomad4 AMR exome AF: 0.00210

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000183

Gnomad4 OTH exome AF: 0.00245

GnomAD4 genome AF: 0.0104 AC: 1580 AN: 152252 Hom.: 33 Cov.: 33 AF XY: 0.00989 AC XY: 736 AN XY: 74454

Gnomad4 AFR AF: 0.0361

Gnomad4 AMR AF: 0.00301

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00945

Alfa AF: 0.00384 Hom.: 4

Bravo AF: 0.0111

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0278 AC: 113

ESP6500EA AF: 0.000119 AC: 1

ExAC AF: 0.00308 AC: 373

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0000546

EpiControl AF: 0.000297

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 08, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.26
Cadd	Benign	21
Dann	Uncertain	0.99
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.54	T;T
MetaRNN	Benign	0.0094	T;T
PrimateAI	Benign	0.32	T
Sift4G	Benign	0.26	T;T
Vest4		0.56
MVP		0.68
GERP RS		-3.2
gMVP		0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs55719241; hg19: chr11-30902837;