11-30903511-T-C

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.4481A>G(p.Lys1494Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0028 in 1,601,380 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (58 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (54 hom.)
• Consequence: DCDC1 NM_001387274.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.762

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]

LOC105376611 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023522973).
• BP6: Variant 11-30903511-T-C is Benign according to our data. Variant chr11-30903511-T-C is described in ClinVar as [Benign]. Clinvar id is 718775.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0147 (2241/152336) while in subpopulation AFR AF= 0.0515 (2141/41560). AF 95% confidence interval is 0.0497. There are 58 homozygotes in gnomad4. There are 1035 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 58 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCDC1	NM_001387274.1	c.4481A>G	p.Lys1494Arg	missense_variant	32/39	ENST00000684477.1
LOC105376611	XR_007062642.1	n.207-10T>C		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCDC1	ENST00000684477.1	c.4481A>G	p.Lys1494Arg	missense_variant	32/39		NM_001387274.1	A2

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 2234 AN: 152218 Hom.: 58 Cov.: 32

Gnomad AFR AF: 0.0515

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

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: 0.000235

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.00382 AC: 876 AN: 229420 Hom.: 21 AF XY: 0.00275 AC XY: 339 AN XY: 123288

Gnomad AFR exome AF: 0.0508

Gnomad AMR exome AF: 0.00227

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000143

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000306

Gnomad OTH exome AF: 0.00209

GnomAD4 exome AF: 0.00155 AC: 2243 AN: 1449044 Hom.: 54 Cov.: 30 AF XY: 0.00130 AC XY: 938 AN XY: 719286

Gnomad4 AFR exome AF: 0.0501

Gnomad4 AMR exome AF: 0.00279

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000179

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.000186

Gnomad4 OTH exome AF: 0.00347

GnomAD4 genome AF: 0.0147 AC: 2241 AN: 152336 Hom.: 58 Cov.: 32 AF XY: 0.0139 AC XY: 1035 AN XY: 74488

Gnomad4 AFR AF: 0.0515

Gnomad4 AMR AF: 0.00386

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00256 Hom.: 7

Bravo AF: 0.0160

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0465 AC: 205

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00445 AC: 540

Asia WGS AF: 0.00289 AC: 10 AN: 3476

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	7.9
Dann	Benign	0.93
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.41	T;T
MetaRNN	Benign	0.0024	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.28	T
REVEL	Benign	0.017
Sift4G	Benign	0.20	T;T
Vest4		0.12
MVP		0.25
ClinPred		0.0012	T
GERP RS		0.45
gMVP		0.031

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34110661; hg19: chr11-30925058;