Genetic Variant KHDRBS2:c.952+33C>A (chr6-61697162-G-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.92

Publications

3 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152688.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KHDRBS2	NM_152688.4	MANE Select	c.952+33C>A	intron	N/A	NP_689901.2	Q5VWX1
KHDRBS2	NM_001350622.2		c.1003+33C>A	intron	N/A	NP_001337551.1
KHDRBS2	NR_146870.2		n.1229+33C>A	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KHDRBS2	ENST00000281156.5	TSL:1 MANE Select	c.952+33C>A	intron	N/A	ENSP00000281156.3	Q5VWX1
KHDRBS2	ENST00000968831.1		c.952+33C>A	intron	N/A	ENSP00000638890.1
KHDRBS2	ENST00000931671.1		c.805+33C>A	intron	N/A	ENSP00000601730.1

Frequencies

GnomAD3 genomes

AF:

0.353

AC:

53628

AN:

151774

Hom.:

10296

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.400

AC:

100186

AN:

250308

AF XY:

0.398

show subpopulations

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 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.:

AF XY:

0.413

AC XY:

260243

AN XY:

630172

show subpopulations

African (AFR)

AF:

0.179

AC:

5217

AN:

29112

American (AMR)

AF:

0.469

AC:

20825

AN:

44370

Ashkenazi Jewish (ASJ)

AF:

0.355

AC:

8778

AN:

24752

East Asian (EAS)

AF:

0.501

AC:

19335

AN:

38600

South Asian (SAS)

AF:

0.330

AC:

26990

AN:

81900

European-Finnish (FIN)

AF:

0.382

AC:

20282

AN:

53064

Middle Eastern (MID)

AF:

0.446

AC:

2396

AN:

5372

European-Non Finnish (NFE)

AF:

0.429

AC:

391098

AN:

912338

Other (OTH)

AF:

0.398

AC:

21158

AN:

53110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

13773

27546

41319

55092

68865

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10954

21908

32862

43816

54770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.353

AC:

53639

AN:

151892

Hom.:

10300

Cov.:

AF XY:

0.351

AC XY:

26052

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.193

AC:

8011

AN:

41466

American (AMR)

AF:

0.409

AC:

6234

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.352

AC:

1222

AN:

3468

East Asian (EAS)

AF:

0.485

AC:

2489

AN:

5132

South Asian (SAS)

AF:

0.321

AC:

1546

AN:

4812

European-Finnish (FIN)

AF:

0.371

AC:

3906

AN:

10534

Middle Eastern (MID)

AF:

0.422

AC:

124

AN:

294

European-Non Finnish (NFE)

AF:

0.424

AC:

28813

AN:

67922

Other (OTH)

AF:

0.387

AC:

816

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1681

3362

5042

6723

8404

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.315

Hom.:

1707

Bravo

AF:

0.352

Asia WGS

AF:

0.334

AC:

1161

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over