2-31200622-G-C

Variant names:

• chr2-31200622-G-C
• rs143870740
• NM_001145122.2:c.555C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001145122.2(CAPN14):​c.555C>G​(p.Leu185Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,390,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L185L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CAPN14 NM_001145122.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486
• Publications: 0 publications found

Genes affected

CAPN14 (HGNC:16664): (calpain 14) Calpains are a family of cytosolic calcium-activated cysteine proteases involved in a variety of cellular processes including apoptosis, cell division, modulation of integrin-cytoskeletal interactions, and synaptic plasticity (Dear et al., 2000 [PubMed 10964513]). CAPN14 belongs to the calpain large subunit family.[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-0.486 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAPN14	NM_001145122.2	c.555C>G	p.Leu185Leu	synonymous_variant	Exon 6 of 22	ENST00000403897.4	NP_001138594.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAPN14	ENST00000403897.4	c.555C>G	p.Leu185Leu	synonymous_variant	Exon 6 of 22	2	NM_001145122.2	ENSP00000385247.3
CAPN14	ENST00000398824.6	n.418C>G		non_coding_transcript_exon_variant	Exon 6 of 22	2		ENSP00000381805.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1390912 Hom.: 0 Cov.: 31 AF XY: 0.00000292 AC XY: 2 AN XY: 685666

African (AFR) AF: 0.00 AC: 0 AN: 31110

American (AMR) AF: 0.00 AC: 0 AN: 33330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24632

East Asian (EAS) AF: 0.00 AC: 0 AN: 35626

South Asian (SAS) AF: 0.00 AC: 0 AN: 77506

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5644

European-Non Finnish (NFE) AF: 0.00000186 AC: 2 AN: 1076264

Other (OTH) AF: 0.00 AC: 0 AN: 57600

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.76
DANN	Benign	0.71
PhyloP100		-0.49
Mutation Taster		=99/1	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: rs143870740; hg19: chr2-31423488; COSMIC: COSV101294838;