6-61697162-G-T

Position:

• chr6-61697162-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_152688.4(KHDRBS2):​c.952+33C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,394,510 control chromosomes in the GnomAD database, including 119,627 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 0.35 (10300 hom., cov: 31)
  • Exomes 𝑓: 0.42 (109327 hom.)
• Consequence: KHDRBS2 NM_152688.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.92

Genes affected

KHDRBS2 (HGNC:18114): (KH RNA binding domain containing, signal transduction associated 2) Predicted to enable mRNA binding activity and poly(A) binding activity. Predicted to be involved in regulation of alternative mRNA splicing, via spliceosome. Predicted to be located in nucleoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

KHDRBS2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KHDRBS2	NM_152688.4	c.952+33C>A		intron_variant		ENST00000281156.5	NP_689901.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KHDRBS2	ENST00000281156.5	c.952+33C>A		intron_variant		1	NM_152688.4	ENSP00000281156.3
KHDRBS2	ENST00000675091.1	n.*108+33C>A		intron_variant				ENSP00000502245.1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53628 AN: 151774 Hom.: 10296 Cov.: 31

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.390

GnomAD3 exomes AF: 0.400 AC: 100186 AN: 250308 Hom.: 20860 AF XY: 0.398 AC XY: 53814 AN XY: 135318

Gnomad AFR exome AF: 0.184

Gnomad AMR exome AF: 0.477

Gnomad ASJ exome AF: 0.352

Gnomad EAS exome AF: 0.490

Gnomad SAS exome AF: 0.325

Gnomad FIN exome AF: 0.377

Gnomad NFE exome AF: 0.422

Gnomad OTH exome AF: 0.411

GnomAD4 exome AF: 0.415 AC: 516079 AN: 1242618 Hom.: 109327 Cov.: 18 AF XY: 0.413 AC XY: 260243 AN XY: 630172

Gnomad4 AFR exome AF: 0.179

Gnomad4 AMR exome AF: 0.469

Gnomad4 ASJ exome AF: 0.355

Gnomad4 EAS exome AF: 0.501

Gnomad4 SAS exome AF: 0.330

Gnomad4 FIN exome AF: 0.382

Gnomad4 NFE exome AF: 0.429

Gnomad4 OTH exome AF: 0.398

GnomAD4 genome AF: 0.353 AC: 53639 AN: 151892 Hom.: 10300 Cov.: 31 AF XY: 0.351 AC XY: 26052 AN XY: 74208

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.387

Alfa AF: 0.318 Hom.: 1694

Bravo AF: 0.352

Asia WGS AF: 0.334 AC: 1161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	14
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555167; hg19: chr6-62407067; COSMIC: COSV55436851;