6-24358255-G-C

Variant names:

• chr6-24358255-G-C
• rs1277349
• ENST00000274766.2:n.1353G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000274766.2(KAAG1):​n.1353G>C variant causes a non coding transcript exon 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: KAAG1 ENST00000274766.2 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.177
• Publications: 1 publications found

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]

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: Labcorp Genetics (formerly Invitae), Orphanet
• nephronophthisis 19

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

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• autosomal recessive nonsyndromic hearing loss 66

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000274766.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAAG1	NR_174942.1		n.1353G>C		non_coding_transcript_exon	Exon 1 of 1
	DCDC2	NM_001195610.2		c.-97-408C>G		intron	N/A	NP_001182539.1
	DCDC2	NM_016356.5	MANE Select	c.-505C>G		upstream_gene	N/A	NP_057440.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KAAG1	ENST00000274766.2	TSL:6	n.1353G>C		non_coding_transcript_exon	Exon 1 of 1
	DCDC2	ENST00000378454.8	TSL:1 MANE Select	c.-505C>G		upstream_gene	N/A	ENSP00000367715.3

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

African (AFR) AF: 0.886 AC: 1947 AN: 2198

American (AMR) AF: 0.971 AC: 1851 AN: 1906

Ashkenazi Jewish (ASJ) AF: 0.993 AC: 2306 AN: 2322

East Asian (EAS) AF: 1.00 AC: 4396 AN: 4396

South Asian (SAS) AF: 0.998 AC: 561 AN: 562

European-Finnish (FIN) AF: 0.997 AC: 17940 AN: 17992

Middle Eastern (MID) AF: 0.997 AC: 299 AN: 300

European-Non Finnish (NFE) AF: 0.983 AC: 38220 AN: 38896

Other (OTH) AF: 0.976 AC: 3891 AN: 3988

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

African (AFR) AF: 0.888 AC: 36820 AN: 41462

American (AMR) AF: 0.972 AC: 14870 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 3453 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5168 AN: 5168

South Asian (SAS) AF: 1.00 AC: 4820 AN: 4822

European-Finnish (FIN) AF: 0.997 AC: 10586 AN: 10618

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.981 AC: 66712 AN: 68032

Other (OTH) AF: 0.962 AC: 2032 AN: 2112

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

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.2
DANN	Benign	0.54
PhyloP100		0.18
PromoterAI		0.024	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1277349; hg19: chr6-24358483;