rs1201494

Positions:

• chr6-61779978-A-G
• chr6-61779978-A-T

Variant summary

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

The ENST00000281156.5(KHDRBS2):​c.811-47214T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 151,902 control chromosomes in the GnomAD database, including 33,532 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 0.66 (33532 hom., cov: 31)
• Consequence: KHDRBS2 ENST00000281156.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.679

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KHDRBS2	NM_152688.4	c.811-47214T>C		intron_variant		ENST00000281156.5	NP_689901.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KHDRBS2	ENST00000281156.5	c.811-47214T>C		intron_variant		1	NM_152688.4	ENSP00000281156	P1
KHDRBS2	ENST00000675091.1	c.811-47214T>C		intron_variant, NMD_transcript_variant				ENSP00000502245

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99666 AN: 151784 Hom.: 33479 Cov.: 31

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.619

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.657 AC: 99774 AN: 151902 Hom.: 33532 Cov.: 31 AF XY: 0.658 AC XY: 48846 AN XY: 74222

Gnomad4 AFR AF: 0.807

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.670

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.703

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.621

Alfa AF: 0.621 Hom.: 3695

Bravo AF: 0.658

Asia WGS AF: 0.677 AC: 2353 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.83
DANN	Benign	0.35

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: rs1201494; hg19: chr6-62489883;