6-61697209-G-C

Variant names:

• chr6-61697209-G-C
• rs145615844
• NM_152688.4:c.938C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152688.4(KHDRBS2):​c.938C>G​(p.Ala313Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,454,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A313V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: KHDRBS2 NM_152688.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.08
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15072304).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KHDRBS2	NM_152688.4	MANE Select	c.938C>G	p.Ala313Gly	missense	Exon 8 of 9	NP_689901.2	Q5VWX1
	KHDRBS2	NM_001350622.2		c.989C>G	p.Ala330Gly	missense	Exon 9 of 10	NP_001337551.1
	KHDRBS2	NR_146870.2		n.1215C>G		non_coding_transcript_exon	Exon 8 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KHDRBS2	ENST00000281156.5	TSL:1 MANE Select	c.938C>G	p.Ala313Gly	missense	Exon 8 of 9	ENSP00000281156.3	Q5VWX1
	KHDRBS2	ENST00000968831.1		c.938C>G	p.Ala313Gly	missense	Exon 8 of 10	ENSP00000638890.1
	KHDRBS2	ENST00000931671.1		c.791C>G	p.Ala264Gly	missense	Exon 7 of 8	ENSP00000601730.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1454932 Hom.: 0 Cov.: 28 AF XY: 0.00000276 AC XY: 2 AN XY: 724284

African (AFR) AF: 0.00 AC: 0 AN: 33338

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39622

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53334

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1105870

Other (OTH) AF: 0.00 AC: 0 AN: 60144

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.031
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		5.1
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.63	N
REVEL	Benign	0.078
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.23	T
Polyphen		0.21	B
Vest4		0.44
MutPred		0.18		Loss of helix (P = 0.0376)
MVP		0.53
MPC		0.062
ClinPred		0.58	D
GERP RS		4.5
Varity_R		0.24
gMVP		0.31
Mutation Taster		=88/12	polymorphism

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

Other links and lift over

dbSNP: rs145615844; hg19: chr6-62407114;