rs143313706

Variant names:

• chr6-24178612-G-A
• rs143313706
• NM_016356.5:c.1044C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-24178612-G-A
• chr6-24178612-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_016356.5(DCDC2):​c.1044C>T​(p.Asp348Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00313 in 1,612,918 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0029 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (29 hom.)
• Consequence: DCDC2 NM_016356.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.237
• Publications: 2 publications found

Genes affected

DCDC2 (HGNC:18141): (doublecortin domain containing 2) This gene encodes a doublecortin domain-containing family member. The doublecortin domain has been demonstrated to bind tubulin and enhance microtubule polymerization. This family member is thought to function in neuronal migration where it may affect the signaling of primary cilia. Mutations in this gene have been associated with reading disability (RD) type 2, also referred to as developmental dyslexia. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jan 2013]

DCDC2 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Ambry Genetics
• isolated neonatal sclerosing cholangitis

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• nephronophthisis 19

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Senior-Boichis syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive nonsyndromic hearing loss 66

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 6-24178612-G-A is Benign according to our data. Variant chr6-24178612-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 466321.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.237 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0029 (441/152016) while in subpopulation AMR AF = 0.00399 (61/15270). AF 95% confidence interval is 0.00319. There are 4 homozygotes in GnomAd4. There are 220 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016356.5. 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
	DCDC2	NM_016356.5	MANE Select	c.1044C>T	p.Asp348Asp	synonymous	Exon 9 of 10	NP_057440.2	Q9UHG0-1
	DCDC2	NM_001195610.2		c.1044C>T	p.Asp348Asp	synonymous	Exon 10 of 11	NP_001182539.1	Q9UHG0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCDC2	ENST00000378454.8	TSL:1 MANE Select	c.1044C>T	p.Asp348Asp	synonymous	Exon 9 of 10	ENSP00000367715.3	Q9UHG0-1
	DCDC2	ENST00000378450.6	TSL:1	c.303C>T	p.Asp101Asp	synonymous	Exon 2 of 3	ENSP00000367711.3	Q9UHG0-2
	DCDC2	ENST00000883243.1		c.1044C>T	p.Asp348Asp	synonymous	Exon 10 of 11	ENSP00000553302.1

Frequencies

GnomAD3 genomes AF: 0.00290 AC: 441 AN: 151898 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00400

Gnomad ASJ AF: 0.0303

Gnomad EAS AF: 0.000966

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.000190

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00316

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00391 AC: 980 AN: 250470 AF XY: 0.00414

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.00231

Gnomad ASJ exome AF: 0.0283

Gnomad EAS exome AF: 0.00109

Gnomad FIN exome AF: 0.000377

Gnomad NFE exome AF: 0.00382

Gnomad OTH exome AF: 0.00393

GnomAD4 exome AF: 0.00315 AC: 4603 AN: 1460902 Hom.: 29 Cov.: 32 AF XY: 0.00329 AC XY: 2390 AN XY: 726752

African (AFR) AF: 0.000299 AC: 10 AN: 33456

American (AMR) AF: 0.00253 AC: 113 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 743 AN: 26066

East Asian (EAS) AF: 0.000529 AC: 21 AN: 39700

South Asian (SAS) AF: 0.00407 AC: 351 AN: 86200

European-Finnish (FIN) AF: 0.000170 AC: 9 AN: 52880

Middle Eastern (MID) AF: 0.00902 AC: 52 AN: 5768

European-Non Finnish (NFE) AF: 0.00273 AC: 3036 AN: 1111754

Other (OTH) AF: 0.00444 AC: 268 AN: 60382

GnomAD4 genome AF: 0.00290 AC: 441 AN: 152016 Hom.: 4 Cov.: 32 AF XY: 0.00296 AC XY: 220 AN XY: 74266

African (AFR) AF: 0.000724 AC: 30 AN: 41452

American (AMR) AF: 0.00399 AC: 61 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0303 AC: 105 AN: 3470

East Asian (EAS) AF: 0.000968 AC: 5 AN: 5166

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4816

European-Finnish (FIN) AF: 0.000190 AC: 2 AN: 10538

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00316 AC: 215 AN: 67986

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.00514 Hom.: 1

Bravo AF: 0.00319

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00534

EpiControl AF: 0.00557

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Autosomal recessive nonsyndromic hearing loss 66;C4015542:Nephronophthisis 19;C4479344:Isolated neonatal sclerosing cholangitis (1)
-	-	1	Autosomal recessive nonsyndromic hearing loss 66;C4479344:Isolated neonatal sclerosing cholangitis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	7.9
DANN	Benign	0.39
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism

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: rs143313706; hg19: chr6-24178840; COSMIC: COSV65828641;