2-98822073-G-C

Position:

• chr2-98822073-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000397899.7(CRACDL):​c.2200C>G​(p.Pro734Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CRACDL ENST00000397899.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00800

Genes affected

CRACDL (HGNC:33454): (CRACD like)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16293857).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRACDL	NM_207362.3	c.2200C>G	p.Pro734Ala	missense_variant	7/10	ENST00000397899.7	NP_997245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRACDL	ENST00000397899.7	c.2200C>G	p.Pro734Ala	missense_variant	7/10	1	NM_207362.3	ENSP00000380996	P1
CRACDL	ENST00000464413.1	n.232C>G		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1400968 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 691472

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000891 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 07, 2023

The c.2200C>G (p.P734A) alteration is located in exon 7 (coding exon 6) of the KIAA1211L gene. This alteration results from a C to G substitution at nucleotide position 2200, causing the proline (P) at amino acid position 734 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	5.4
DANN	Uncertain	0.99
DEOGEN2	Benign	0.071	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.044
Sift	Benign	0.25	T
Sift4G	Benign	0.39	T
Polyphen		1.0	D
Vest4		0.17
MutPred		0.28		Loss of helix (P = 0.0304);
MVP		0.061
ClinPred		0.72	D
GERP RS		2.6
Varity_R		0.039
gMVP		0.065

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: rs779381800; hg19: chr2-99438536;