NM_001013838.3:c.6C>T

Variant names:

• chr16-67645252-C-T
• NM_001013838.3:c.6C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001013838.3(CARMIL2):​c.6C>T​(p.Ala2Ala) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CARMIL2 NM_001013838.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.309
• Publications: 0 publications found

Genes affected

CARMIL2 (HGNC:27089): (capping protein regulator and myosin 1 linker 2) This gene encodes a member of the CARMIL (capping protein, Arp2/3, myosin-I linker) family of proteins. The encoded protein interacts with and negatively regulates the heterodimeric capping protein and promotes cell migration. Reduced expression of this gene has been observed in human psoriasis patients. Mutations in this gene cause a human immunodeficiency syndrome characterized by smooth muscle tumors and impaired T-cell function. [provided by RefSeq, May 2017]

CARMIL2 Gene-Disease associations (from GenCC):

• severe combined immunodeficiency due to CARMIL2 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

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=-0.41).
• BP6: Variant 16-67645252-C-T is Benign according to our data. Variant chr16-67645252-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2879138.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.309 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013838.3. 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
	CARMIL2	NM_001013838.3	MANE Select	c.6C>T	p.Ala2Ala	synonymous	Exon 1 of 38	NP_001013860.1	Q6F5E8-1
	CARMIL2	NM_001438835.1		c.6C>T	p.Ala2Ala	synonymous	Exon 1 of 39	NP_001425764.1
	CARMIL2	NM_001438244.1		c.6C>T	p.Ala2Ala	synonymous	Exon 1 of 39	NP_001425173.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARMIL2	ENST00000334583.11	TSL:1 MANE Select	c.6C>T	p.Ala2Ala	synonymous	Exon 1 of 38	ENSP00000334958.5	Q6F5E8-1
	CARMIL2	ENST00000545661.5	TSL:1	c.6C>T	p.Ala2Ala	synonymous	Exon 1 of 38	ENSP00000441481.1	Q6F5E8-2
	CARMIL2	ENST00000696175.1		c.6C>T	p.Ala2Ala	synonymous	Exon 1 of 39	ENSP00000512465.1	A0A8Q3SII9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1447572 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 718778

African (AFR) AF: 0.00 AC: 0 AN: 33222

American (AMR) AF: 0.00 AC: 0 AN: 43186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25670

East Asian (EAS) AF: 0.00 AC: 0 AN: 39212

South Asian (SAS) AF: 0.00 AC: 0 AN: 83826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50722

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106194

Other (OTH) AF: 0.00 AC: 0 AN: 59790

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	12
DANN	Benign	0.96
PhyloP100		-0.31
PromoterAI		-0.038	Neutral

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

hg19: chr16-67679155;