rs197388

Variant names:

• chr1-111754860-A-T
• rs197388
• ENST00000412270.1:n.222+428T>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198926.2(INKA2):​c.12+841T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,208 control chromosomes in the GnomAD database, including 6,598 homozygotes. 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: 𝑓 0.26 (6596 hom., cov: 33)
  • Exomes 𝑓: 0.23 (2 hom.)
• Consequence: INKA2 NM_198926.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293

Genes affected

ENSG00000284830 (HGNC:):

INKA2 (HGNC:28045): (inka box actin regulator 2) Enables protein kinase binding activity. Predicted to be involved in negative regulation of catalytic activity. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DDX20 (HGNC:2743): (DEAD-box helicase 20) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which has an ATPase activity and is a component of the survival of motor neurons (SMN) complex. This protein interacts directly with SMN, the spinal muscular atrophy gene product, and may play a catalytic role in the function of the SMN complex on RNPs. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INKA2	NM_198926.2	c.12+841T>A		intron_variant	Intron 1 of 1		NP_945120.1
LOC101928718	NR_125963.1	n.222+428T>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000284830	ENST00000412270.1	n.222+428T>A		intron_variant	Intron 1 of 2	1
INKA2	ENST00000444059.2	n.124+841T>A		intron_variant	Intron 1 of 1	1
DDX20	ENST00000679724	c.-64A>T		5_prime_UTR_variant	Exon 1 of 12			ENSP00000505857.1
ENSG00000284830	ENST00000625113.1	n.678T>A		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39463 AN: 152060 Hom.: 6585 Cov.: 33

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0402

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.233 AC: 7 AN: 30 Hom.: 2 Cov.: 0 AF XY: 0.188 AC XY: 3 AN XY: 16

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.583

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.260 AC: 39529 AN: 152178 Hom.: 6596 Cov.: 33 AF XY: 0.254 AC XY: 18875 AN XY: 74410

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.0401

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.246

Alfa AF: 0.238 Hom.: 653

Bravo AF: 0.265

Asia WGS AF: 0.111 AC: 385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs197388; hg19: chr1-112297482;