rs1277349

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr6-24358255-G-A
• chr6-24358255-G-C
• chr6-24358255-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000274766.2(KAAG1):​n.1353G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KAAG1 ENST00000274766.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KAAG1	NR_174942.1	n.1353G>A		non_coding_transcript_exon_variant	Exon 1 of 1
DCDC2	NM_001195610.2	c.-97-408C>T		intron_variant	Intron 1 of 10		NP_001182539.1
DCDC2	NM_016356.5	c.-505C>T		upstream_gene_variant		ENST00000378454.8	NP_057440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KAAG1	ENST00000274766.2	n.1353G>A		non_coding_transcript_exon_variant	Exon 1 of 1	6
DCDC2	ENST00000378454.8	c.-505C>T		upstream_gene_variant		1	NM_016356.5	ENSP00000367715.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 72574 Hom.: 0 Cov.: 1 AF XY: 0.00 AC XY: 0 AN XY: 36054

African (AFR) AF: 0.00 AC: 0 AN: 2200

American (AMR) AF: 0.00 AC: 0 AN: 1906

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2322

East Asian (EAS) AF: 0.00 AC: 0 AN: 4396

South Asian (SAS) AF: 0.00 AC: 0 AN: 562

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17992

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 300

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 38908

Other (OTH) AF: 0.00 AC: 0 AN: 3988

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.5
DANN	Benign	0.34
PhyloP100		0.18
PromoterAI		-0.00080	Neutral

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;