chr6-24358255-G-C

Position:

• chr6-24358255-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001195610.2(DCDC2):​c.-97-408C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.966 in 224,744 control chromosomes in the GnomAD database, including 105,029 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.96 (69875 hom., cov: 31)
  • Exomes 𝑓: 0.98 (35154 hom.)
• Consequence: DCDC2 NM_001195610.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.177

Genes affected

KAAG1 (HGNC:21031): (kidney associated DCDC2 antisense RNA 1)

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]

KAAG1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 6-24358255-G-C is Benign according to our data. Variant chr6-24358255-G-C is described in ClinVar as [Benign]. Clinvar id is 1255344.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCDC2	NM_001195610.2	c.-97-408C>G		intron_variant			NP_001182539.1
KAAG1	NR_174942.1	n.1353G>C		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KAAG1	ENST00000274766.2	n.1353G>C		non_coding_transcript_exon_variant	1/1	6	NM_181337.4

Frequencies

GnomAD3 genomes AF: 0.957 AC: 145576 AN: 152066 Hom.: 69841 Cov.: 31

Gnomad AFR AF: 0.888

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.972

Gnomad ASJ AF: 0.995

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 0.997

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.981

Gnomad OTH AF: 0.962

GnomAD4 exome AF: 0.984 AC: 71411 AN: 72560 Hom.: 35154 Cov.: 1 AF XY: 0.985 AC XY: 35498 AN XY: 36046

Gnomad4 AFR exome AF: 0.886

Gnomad4 AMR exome AF: 0.971

Gnomad4 ASJ exome AF: 0.993

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.998

Gnomad4 FIN exome AF: 0.997

Gnomad4 NFE exome AF: 0.983

Gnomad4 OTH exome AF: 0.976

GnomAD4 genome AF: 0.957 AC: 145664 AN: 152184 Hom.: 69875 Cov.: 31 AF XY: 0.960 AC XY: 71408 AN XY: 74416

Gnomad4 AFR AF: 0.888

Gnomad4 AMR AF: 0.972

Gnomad4 ASJ AF: 0.995

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 0.997

Gnomad4 NFE AF: 0.981

Gnomad4 OTH AF: 0.962

Alfa AF: 0.974 Hom.: 3927

Bravo AF: 0.951

Asia WGS AF: 0.993 AC: 3453 AN: 3478

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

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.2
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1277349; hg19: chr6-24358483;